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Prequalification as a Gateway to Global Markets & Performance of WHO Prequalification of Medicines Programme CPhI China 2014 Shanghai, 26‒28 June 2014 Jacqueline Sawyer. page n ° 2. WHO medicines prequalification | CPhI China | June 2014. Outline of this presentation: - PowerPoint PPT Presentation
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Prequalification as a Gateway to Global Markets
&
Performance of WHO Prequalification of Medicines Programme
CPhI China 2014
Shanghai, 26‒28 June 2014
Jacqueline Sawyer
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
page n °2
WHO medicines prequalification | CPhI China | June 2014
Part 1
page n 3 WHO medicines prequalification | CPhI China | June 2014
Direct and indirect value/benefits
page n °4
WHO medicines prequalification | CPhI China | June 2014
Direct value
Indirect value
PQP
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)
Institutional market sizes
page n °5
WHO medicines prequalification | CPhI China | June 2014
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
TB• Total market estimate for low- and middle-income countries: US$ 730
million • Donor market estimate: $200 million
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. 2013UNITAID, 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.
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
page n °6
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
page n °7
WHO medicines prequalification | CPhI China | June 2014
Donor medical contraceptives: market growth
page n °8
WHO medicines prequalification | CPhI China | June 2014
Quality is key to accessing institutional marketsGrowing 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-unitaid-purchased-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-now-eligible-for-usaid-procurement.html
page n °9
WHO medicines prequalification | CPhI China | June 2014
Quality also key to going beyond institutional markets
page n °10
WHO medicines prequalification | CPhI China | June 2014
"Missing" or few products: examples
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
page n °11
WHO medicines prequalification | CPhI China | June 2014
MEDICINES FOR REPRODUCTIVE HEALTH
2. Injectable hormonal contraceptivesNumber of
individual FPPs prequalified
Number of individual FPPs
under assessmentMedroxyprogesterone acetate, depot injection 150 mg/ml, in 1-ml vial 1Medroxyprogesterone acetate + estradiol cypronate, injection 25 mg + 5 mgNorethisterone enanthate, injection 200 mg 1Norethisterone enanthate + estradiol valerate, injection 50 mg + 5 mg
1.3. Protease Inhibitors
Atazanavir, capsule 150 mg 2Atazanavir, capsule 300 mg 1 1Darunavir, tablet 400 mgDarunavir, tablet 600 mg 1Darunavir, tablet 800 mgRitonavir, tablet (heat-stable) 100 mg 2 2
Number of individual FPPs
prequalified
Number of individual FPPs
under assessment1. Antiretrovirals as single-ingredient formulations for use in adults and adolescents
But what investment is needed to attain PQ approval?
page n °12
WHO medicines prequalification | CPhI China | June 2014
http://apps.who.int/prequal/info_press/documents/WHO_Prequalification_WHY.pdf
Bioequivalence studies
page n °13
WHO medicines prequalification | CPhI China | June 2014
Formulation development
page n °14
WHO medicines prequalification | CPhI China | June 2014
page n °15 WHO medicines prequalification | CPhI China | June 2014
• 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
Investment needed to attain prequalification:Will vary depending on experience of company
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.
page n °16 WHO medicines prequalification | CPhI China | June 2014
Useful informationCurrent 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
page n °17 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 vaccinesCopenhagen, 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/
page n °18 WHO medicines prequalification | CPhI China | June 2014
Part 2
page n °19
WHO medicines prequalification | CPhI China | June 2014
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
page n °20
WHO medicines prequalification | CPhI China | June 2014
Perceptions of PQP of FPP manufacturers (1)
page n °22
WHO medicines prequalification | CPhI China | June 2014
0%
10%
20%
30%
40%
50%
60%
70%
1 2 3 4 5 6 7
Per
cent
of
Res
po
nden
ts
Agree Less --- Agree More
The benefits of participating in WHO PQP outweigh any investments my company may have to make in corrective
actions required by WHO
Perceptions of PQP of FPP manufacturers (2)
page n °8
WHO medicines prequalification | CPhI China | June 2014
0%
10%
20%
30%
40%
50%
60%
70%
1 2 3 4 5 6 7
Per
cent
of
Res
po
nden
ts
Agree Less --- Agree More
The reputation of my company is enhanced by participating in WHO PQP
Perceptions of PQP of FPP manufacturers (3)
page n °23
WHO medicines prequalification | CPhI China | June 2014
0%
10%
20%
30%
40%
50%
60%
70%
1 2 3 4 5 6 7
Per
cent
of
Res
po
nden
ts
Agree Less --- Agree More
Participating in WHO PQP increases the internal capabilities of my company
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.
page n °24
WHO medicines prequalification | CPhI China | June 2014
Timeline to prequalification
page n °25
WHO medicines prequalification | CPhI China | June 2014
2009 2010 2011 2012Median number of days (including range and inter-quartile range) from receipt of FPP application for prequalification to completion of initial screening of the dossier
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)
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
276(29-850)
(388-185 =203)
266(15-914)
(475-127 =348)
267(44-548)
(356-182 =174)
296 (5-875)
(444-190 =250)
full dossiers:
198(101-501)
(307.5-136 =171.5)
SRA-approved dossiers:
15 (2-58)
(26-9.5 =16.5)
all dossiers:
58
Median number of stop clock days from completion of screening and acceptance of FPP dossier for assessment to completion of dossier assessment
409(20-1872)
(479-169 =310)
414(0-2394)
(892-217 =675)
514(2-1187)
(681-245 =436)
344 (5-1331)
861-132 =729)
full dossiers:
304(144-1451)(569.75 - 215.25 =354.5)
SRA-approved dossiers:
26 (0-394) (70.5-14 =56.5)
all dossiers:
194
2013
8(0-35)
(13-3=10)
Improvements to timeline to prequalification (1)
page n °26
WHO medicines prequalification | CPhI China | June 2014
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
full dossiers: 198
SRA-approved dossiers:
15
all dossiers:
58
Median number of stop clock days from completion of screening and acceptance of FPP dossier for assessment to completion of dossier assessment
full dossiers: 304
SRA-approved dossiers:
26
all dossiers:
194
Total time to PQ 598 97 332
Median number of days (including range and inter-quartile range) from receipt of FPP variation to completion of the assessment
2013
8
23
Time to prequalification 2009‒2013: median total time, median WHO time, median manufacturers’ time
Improvements to timeline to prequalification (2)
page n °26
WHO medicines prequalification | CPhI China | June 2014
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
full dossiers: 198
SRA-approved dossiers:
15
all dossiers:
58
Median number of stop clock days from completion of screening and acceptance of FPP dossier for assessment to completion of dossier assessment
full dossiers: 304
SRA-approved dossiers:
26
all dossiers:
194
Total time to PQ 598 97 332
Median number of days (including range and inter-quartile range) from receipt of FPP variation to completion of the assessment
2013
8
23
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
page n °28
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
page n °29
WHO medicines prequalification | CPhI China | June 2014
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