Prequalification as a Gateway to Global Markets &

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

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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

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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

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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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Donor medical contraceptives: market growth

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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

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http://www.theglobalfund.org/en/procurement/quality/pharmaceutical/

http://www.unitaid.eu/en/resources/results/9-uncategorised/437-quality-assurance-for-all-unitaid-purchased-products




http://www.stoptb.org/gdf/drugsupply/quality_sourcing_process.asp




http://www.msf.org/msf-drugs-procurement

http://www.msf.org/msf-drugs-procurement

http://www.rhsupplies.org/nc/news/newsview/article/who-prequalified-hormonal-contraceptives-now-eligible-for-usaid-procurement.html

http://www.rhsupplies.org/nc/news/newsview/article/who-prequalified-hormonal-contraceptives-now-eligible-for-usaid-procurement.html

Quality also key to going beyond institutional markets

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"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

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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


prequalified


under assessment1. Antiretrovirals as single-ingredient formulations for use in adults and adolescents

But what investment is needed to attain PQ approval?

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http://apps.who.int/prequal/info_press/documents/WHO_Prequalification_WHY.pdf

Bioequivalence studies

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Formulation development

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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.


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


http://apps.who.int/prequal/info_applicants/eoi/FPPs_APIs_invited.xlsx

http://apps.who.int/prequal/info_applicants/eoi/FPPs_APIs_invited.xlsx

http://apps.who.int/hiv/amds/price/hdd/

http://apps.who.int/hiv/amds/price/hdd/

http://www.theglobalfund.org/en/procurement/pqr

http://utw.msfaccess.org/downloads/documents

http://www.msfaccess.org/content/dr-tb-drugs-under-microscope3rd-edition

http://www.msfaccess.org/content/dr-tb-drugs-under-microscope3rd-edition

https://supply.unicef.org/

https://supply.unicef.org/

http://www.stoptb.org/gdf/drugsupply/pc2.asp

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-TB_Dx_Landscape-Update_Dec%202013.pdf

http://www.unitaid.eu/images/marketdynamics/publications/UNITAID-MalariaMedicinesLandscape-2013_DEC.pdf



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/


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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Perceptions of PQP of FPP manufacturers (1)

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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


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0%

10%

20%

30%

40%

50%

60%

70%

1 2 3 4 5 6 7

Per

cent

of

Res

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nden

ts


The reputation of my company is enhanced by participating in WHO PQP


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0%

10%

20%

30%

40%

50%

60%

70%

1 2 3 4 5 6 7

Per

cent

of

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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.

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Timeline to prequalification

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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)


26 (0-394) (70.5-14 =56.5)

all dossiers:

194

2013

8(0-35)

(13-3=10)

Improvements to timeline to prequalification (1)

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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


15

all dossiers:

58


full dossiers: 304


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)

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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


15

all dossiers:

58


full dossiers: 304


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

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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

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Documents

Prequalification as a Gateway to Global Markets &