1. No category

Prequalification as a Gateway to Global
Markets
&
Performance of WHO Prequalification of
Medicines Programme
CPhI China 2014
Shanghai, 26‒28 June 2014
Jacqueline Sawyer
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WHO medicines prequalification | CPhI China | June 2014
Outline of this presentation:
Part 1: WHO prequalification as a gateway to global
markets
• Institutional market sizes: current and future
• Quality assurance as a prerequisite
• Investment needed to attain prequalification
• Decision process regarding whether to submit an
application for WHO evaluation
Part 2: Performance of WHO Medicines Prequalification
• Customer orientation
• Improvements to WHO Medicines Prequalification
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WHO medicines prequalification | CPhI China | June 2014
Part 1
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WHO medicines prequalification | CPhI China | June 2014
Direct and indirect value/benefits
Direct value
PQP
Indirect value
Access to donor-sponsored markets

Improved quality of all products

Facilitated and faster regulatory approval in a range of
countries (fewer inspections)

Possibility of assistance from expert consultants (GMP,
dossier)

Enhanced technical and organizational capabilities and
chance of succeeding with submissions to SRAs

Higher margins (non-institutional markets)

Increased market share

Contract manufacturing for local markets

Promotion of prequalified APIs

Image (internal and external)
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WHO medicines prequalification | CPhI China | June 2014
Institutional market sizes
HIV / AIDS
•
•
2012 market size antiretrovirals (ARVs): about US$ 1.5 billion
End 2012 about 10 million patients were treated with ARVs with about 29
million patients that should be treated (2013 guidelines)
Malaria
•
•
Current market size antimalarials: US$ 300 million
Steady growth is expected — as older, ineffective treatments phased out
and higher proportion of patients given WHO-recommended 1st-line
treatment — in market for artemisinin-based combination therapies
•
Total market estimate for low- and middle-income countries: US$ 730
million
Donor market estimate: $200 million
TB
•


•
1st-line anti-TB medicines: US$80 mill
2nd-line: About US$120 mill
1st-line market should remain stable while 2nd-line market should expand
with improved detection of multidrug-resistant TB
Sources: UNITAID, 2014. HIV Medicines Technology and Market Landscape.
Camponeschi G et al. An overview of the antiretroviral market. Current Opinion in HIV and AIDS. 2013
UNITAID, 2013. Tuberculosis Medicines Technology and Market Landscape.
UNITAID, January 2012. HIV, Tuberculosis and Malaria Medicines Landscape. Progress report on emerging
issues and potential opportunities to improve access.
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WHO medicines prequalification | CPhI China | June 2014
HIV/AIDS, TB, malaria: the opportunity
•
•
•
•
•
•
•
Leading newer 1st-line medicines represent attractive market
opportunities; prices still reasonable
Many opportunities in new formulations of leading medicines and
several niche market opportunities, e.g. paediatric medicines
Price per tablet relatively stable for the leading 1st-line antimalarial
New entrant has opportunity to capture significant market share of
antimalarials market
Only a few leading antimalarial products to focus on
1st-line TB market is a stable market with stable prices
2nd-line TB market is growing with stable prices for leading 2nd-line
products
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WHO medicines prequalification | CPhI China | June 2014
Market for reproductive health medicines
• RH market seen as less competitive than e.g. ARV or anti-TB markets
(i.e. higher profit margin)
• Consumer focused – brand awareness

Often tenders request a (generic) branded product, especially at
Ministry of Health level

Nongovernmental organizations can be loyal customers, often
create their own brands

Some manufacturers create new brands for the institutional / donor
market
• Many manufacturers focused on RH alone
• Planning by government or agencies usually poor; “family planning
mindset” needed
• Ramifications of poor quality are not directly life or death and
governments and local procurers often do not fully appreciate the
benefits of quality
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WHO medicines prequalification | CPhI China | June 2014
Donor medical contraceptives: market growth
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WHO medicines prequalification | CPhI China | June 2014
Quality is key to accessing institutional markets
Growing number of international organizations procuring or funding procurement of
medicines specify that medicines procured must be approved by stringent regulatory
authority or WHO-prequalified, e.g.:
• http://www.theglobalfund.org/en/procurement/quality/pharmaceutical/#General
• http://www.unitaid.eu/en/resources/results/9-uncategorised/437-quality-assurance-for-all-unitaidpurchased-products
• http://www.unfpa.org/public/home/procurement/pid/10863
• http://www.unicef.org/supply/index_41948.html
• http://www.stoptb.org/gdf/drugsupply/quality_sourcing_process.asp
• http://www.msf.org/msf-drugs-procurement
Even USAID (for hormonal contraceptives)
• http://www.rhsupplies.org/nc/news/newsview/article/who-prequalified-hormonal-contraceptives-noweligible-for-usaid-procurement.html
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WHO medicines prequalification | CPhI China | June 2014
Quality also key to going beyond institutional markets
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WHO medicines prequalification | CPhI China | June 2014
"Missing" or few products: examples
1. Antiretrovirals as single-ingredient formulations for use in adults and adolescents
Number of
individual FPPs
prequalified
Number of
individual FPPs
under assessment
2
1
1
1.3. Protease Inhibitors
Atazanavir, capsule 150 mg
Atazanavir, capsule 300 mg
Darunavir, tablet 400 mg
Darunavir, tablet 600 mg
Darunavir, tablet 800 mg
Ritonavir, tablet (heat-stable) 100 mg
1
2
2
See list of all APIs and FPPs invited for prequalification, and number prequalified or currently under assessment, per product:
http://apps.who.int/prequal/info_applicants/eoi/FPPs_APIs_invited.xlsx
MEDICINES FOR REPRODUCTIVE HEALTH
2. Injectable hormonal contraceptives
Medroxyprogesterone acetate, depot injection 150 mg/ml, in 1-ml vial
Medroxyprogesterone acetate + estradiol cypronate, injection 25 mg + 5 mg
Norethisterone enanthate, injection 200 mg
Norethisterone enanthate + estradiol valerate, injection 50 mg + 5 mg
Number of
individual FPPs
prequalified
1
1
Number of
individual FPPs
under assessment
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WHO medicines prequalification | CPhI China | June 2014
But what investment is needed to attain PQ approval?
http://apps.who.int/prequal/info_press/documents/WHO_Prequalification_WHY.pdf
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Bioequivalence studies
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Formulation development
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WHO medicines prequalification | CPhI China | June 2014
Investment needed to attain prequalification:
Will vary depending on experience of company
•
•
•
•
•
Manufacturers experienced in
dealing with global regulatory
agencies will have fewer
investments in both capital and
formulation development
Manufacturers with existing
dossiers will have fewer
investments to make
Formulation development may be
necessary and depends upon the
complexity of the medicine
Companies without a WHO
GMP-standard facility, will require
renovations to meet GMP
standards
Companies new to the
pharmaceutical industry will have
to make major investments in
capital infrastructure
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WHO medicines prequalification | CPhI China | June 2014
The business decision process
A “PQ strategy” should not be seen in isolation but as a part of the company’s
broader strategy that takes into account:
 geographic portfolio
 product portfolio
 target markets
 the type of investments required (human and financial)
 company skills
 market size and future demand
 revenue potential
 cost of applying for PQP
 schedule
 profit potential
 degree of risk: no guarantee of securing tenders; forecasting can be
challenging; expected time to approval (especially for small companies
with limited SRA experience); the higher cost of producing quality
products (e.g. 5‒10% greater than for non-quality-assured products).
and is supported at highest level of company.
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WHO medicines prequalification | CPhI China | June 2014
Useful information
Current treatment recommendations:
Standard treatment guidelines for eligible medicines referenced in WHO invitations for EOI. Indications, dosage &
recommended alternatives.
Competitors in the market and in the pipeline:
WHO PQP list of prequalified products & products under assessment for WHO-prequalification:
http://apps.who.int/prequal/info_applicants/eoi/FPPs_APIs_invited.xlsx
Volumes procured, and at what prices: Historical pricing information can give an indication on where the markets
are going.
WHO AMDS Global Price Reporting Mechanism (HIV drugs): http://apps.who.int/hiv/amds/price/hdd/
Global Fund Price and Quality Reporting mechanism (PQR) (HIV, TB, malaria drugs):
www.theglobalfund.org/en/procurement/pqr
Médecins Sans Frontières (MSF) – Untangling the Web of Antiretroviral Price Reductions.
http://utw.msfaccess.org/downloads/documents
MSF –TB drugs under the microscope. http://www.msfaccess.org/content/dr-tb-drugs-under-microscope3rd-edition
Current pricing information for some products: UNICEF product catalogue with indicative prices :
https://supply.unicef.org/; Global Drug Facility product catalogue http://www.stoptb.org/gdf/drugsupply/pc2.asp
Expected market outlook:
UNITAID market landscape and technical report for key health products. E.g. HIV/AIDS medicines technology and
market landscape, TB medicines technology and market landscape, malaria medicines landscape
http://www.unitaid.eu/images/marketdynamics/publications/HIV-Meds-Landscape-March2014.pdf
http://www.unitaid.eu/images/marketdynamics/publications/UNITAID-TB_Dx_Landscape-Update_Dec%202013.pdf
http://www.unitaid.eu/images/marketdynamics/publications/UNITAID-MalariaMedicinesLandscape-2013_DEC.pdf
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WHO medicines prequalification | CPhI China | June 2014
Joint WHO-UNICEF-UNFPA meeting with manufacturers and
suppliers of diagnostic products, finished pharmaceutical
products, active pharmaceutical ingredients and vaccines
Copenhagen, Denmark, from 22 to 25 September 2014
The meeting will cover:
• market demand and product priorities
• new product development
• updates on WHO prequalification procedures and guidelines
• procurement policies of international procurement agencies and major donors
• Day 3 of the meeting will focus on medicines and diagnostics for reproductive
health (including markets, product development and quality issues).
Manufacturers will have the opportunity to meet with assessment and inspection
teams to discuss potential or current applications for evaluation), and with members
of the procurement teams of UNICEF and UNFPA.
Further information available on PQP website: http://apps.who.int/prequal/
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Part 2
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Surveys and qualitative research
•
•
Client focus: understanding perspective of manufacturers

Survey: finished pharmaceutical product (FPP) manufacturers in 2010

Investigation into benefits of WHO prequalification for manufacturers of medicines for
HIV/AID, TB and malaria in 2011

Qualitative research: active pharmaceutical ingredient manufacturers in 2012

Investigation into differences, with respect to prequalification, between manufacturers of
HIV/TB/malaria medicines and manufacturers of reproductive health medicines in 2012

Research into antiretroviral supply/market
Improving WHO prequalification service

Follow up from survey research

Incremental improvement

Innovation

Diagnostics, medicines and vaccines prequalification merged into a single unit
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WHO medicines prequalification | CPhI China | June 2014
Perceptions of PQP of FPP manufacturers (1)
The benefits of participating in WHO PQP outweigh any
investments my company may have to make in corrective
actions required by WHO
Percent of Respondents
70%
60%
50%
40%
30%
20%
10%
0%
1
2
3
4
5
 Agree Less --- Agree More 
6
7
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WHO medicines prequalification | CPhI China | June 2014
Perceptions of PQP of FPP manufacturers (2)
The reputation of my company is enhanced by participating
in WHO PQP
Percent of Respondents
70%
60%
50%
40%
30%
20%
10%
0%
1
2
3
4
5
 Agree Less --- Agree More 
6
7
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WHO medicines prequalification | CPhI China | June 2014
Perceptions of PQP of FPP manufacturers (3)
Participating in WHO PQP increases the internal
capabilities of my company
Percent of Respondents
70%
60%
50%
40%
30%
20%
10%
0%
1
2
3
4
5
 Agree Less --- Agree More 
6
7
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WHO medicines prequalification | CPhI China | June 2014
Not all was good….
E.g. Question 7B.4: In responding to the statement "when it comes to providing an efficient
process to resolve issues and questions raised during the assessment of product dossiers",
manufacturers have indicated that PQP does not meet their minimum expectations.
A paragraph advising manufacturers what action they can take in the event of a
disagreement was added to each assessment and inspection letter sent by the team to
manufacturers.
E.g. Question 18.7: When asked how strongly they agree or disagree with the statement "WHO
GMP requirements are more stringent than EU or US FDA GMP requirements", the majority of
manufacturers indicated that they were more stringent
WHO does not wish to be perceived as more stringent than a stringent regulatory
authority. Comments from manufacturers in the survey did not help to identify the
reasons for the perception. An agenda item to discuss this was included in a meeting on
GMP with manufacturers in 2011. No specific areas of stringency were identified. In fact,
WHO was commended for having guidelines to clarify GMP requirements. This is seen as
helpful to manufacturers.
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WHO medicines prequalification | CPhI China | June 2014
Timeline to prequalification
Median number of days (including
range and inter-quartile range) from
receipt of FPP application for
prequalification to completion of
initial screening of the dossier
Median number of days (including
range and inter-quartile range) from
completion of screening and
acceptance of FPP dossier for
assessment to completion of
dossier assessment, minus "stop
clock" time
Median number of stop clock days
from completion of screening and
acceptance of FPP dossier for
assessment to completion of
dossier assessment
2009
2010
2011
2012
2013
28
(0-58)
(32-6=26)
7
(0-48)
(20-0=20)
11.5
(0-95)
(15-7=8)
11.5
(0-34)
(16-6.5=9.5)
8
(0-35)
(13-3=10)
276
(29-850)
(388-185 =203)
409
(20-1872)
(479-169 =310)
266
(15-914)
(475-127 =348)
414
(0-2394)
(892-217 =675)
267
(44-548)
(356-182 =174)
514
(2-1187)
(681-245 =436)
296
(5-875)
(444-190 =250)
344
(5-1331)
861-132 =729)
full
dossiers:
198
(101-501)
(307.5-136
=171.5)
full
dossiers:
304
(144-1451)
(569.75 215.25
=354.5)
SRAapproved
dossiers:
15
(2-58)
(26-9.5
=16.5)
SRAapproved
dossiers:
26
(0-394)
(70.5-14
=56.5)
all
dossiers:
58
all
dossiers:
194
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WHO medicines prequalification | CPhI China | June 2014
Improvements to timeline to prequalification (1)
Time to prequalification
2009‒2013: median total time,
median WHO time, median
manufacturers’ time
2013
8
Median number of days from receipt of FPP application for prequalification to
completion of initial screening of the dossier
Median number of days from completion of screening and acceptance of FPP dossier
for assessment to completion of dossier assessment, minus "stop clock" time
Median number of stop clock days from completion of screening and acceptance of
FPP dossier for assessment to completion of dossier assessment
Total time to PQ
Median number of days (including range and inter-quartile range) from receipt of FPP
variation to completion of the assessment
full dossiers:
198
full dossiers:
304
598
SRA-approved
dossiers:
15
SRA-approved
dossiers:
26
97
23
all
dossiers:
58
all
dossiers:
194
332
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WHO medicines prequalification | CPhI China | June 2014
Improvements to timeline to prequalification (2)
2013
8
Median number of days from receipt of FPP application for prequalification to
completion of initial screening of the dossier
Median number of days from completion of screening and acceptance of FPP dossier
for assessment to completion of dossier assessment, minus "stop clock" time
Median number of stop clock days from completion of screening and acceptance of
FPP dossier for assessment to completion of dossier assessment
Total time to PQ
Median number of days (including range and inter-quartile range) from receipt of FPP
variation to completion of the assessment
full dossiers:
198
full dossiers:
304
598
SRA-approved
dossiers:
15
SRA-approved
dossiers:
26
97
23
all
dossiers:
58
all
dossiers:
194
332
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WHO medicines prequalification | CPhI China | June 2014
How were the improvements achieved?
• Better guidance, e.g.:

Guidelines on submission of documentation for a multisource product for the WHO
Prequalification of Medicines Programme: quality part
• Specific guidance, e.g.:

Additional guidance for submission of applications for prequalification of zinc sulfate
tablets and zinc sulfate oral liquid

Guidance on bioequivalence studies for reproductive health medicines

Questions and answers on magnesium sulfate injection applications
• Engage and communicate:

Assessment team is accessible and open to consultation pre-submission and after
submissionDuring inspections inspection team will review manufacturer GMP plans:
saves manufacturers time (and expense)

Training workshops, annual meeting with manufacturers
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WHO medicines prequalification | CPhI China | June 2014
In summary
• Institutional market sizes offer many opportunities
• Those products need to be quality-assured
• Prequalified = quality-assured
• WHO Prequalification Programme offers guidance
and support to manufacturers who are committed to
attaining prequalification of their products.
With many thanks for your attention