supply and quality of antimalarial medicines and diagnostics: introduction of issues dr andrea...
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Supply and quality of antimalarial Supply and quality of antimalarial medicines and diagnostics: medicines and diagnostics: introduction of issuesintroduction of issues
Dr Andrea Bosman Dr Andrea Bosman Global Malaria ProgrammeGlobal Malaria Programme
Geneva, 9 July 2009Geneva, 9 July 2009Geneva, 9 July 2009Geneva, 9 July 2009
RBM Case Management Working Group (CMWG)RBM Case Management Working Group (CMWG)
ofof
9 July 2009 2 |GLOBAL
MALARIA PROGRAMME
The built-in chemical instability of artemisinin and its derivatives, necessary for their biological action, causes pharmaceutical problems both in the manufacturing process and in the co-formulation with other compounds. The problems of instability are accelerated under tropical conditions.
The requirement for observing stringent quality manufacturing standards are particularly important for these compounds, for which manufacturers and national regulatory authorities have limited experience.
Differences in product quality selection criteria create opportunities for sub-standard artemisinin-based antimalarial medicines to access international funds for procurement, and discourage compliance with more stringent quality standards.
Quality requirements of artemisinin-based antimalarial medicinesQuality requirements of artemisinin-based antimalarial medicines
9 July 2009 3 |GLOBAL
MALARIA PROGRAMME
UNICEF/WHO tender criteria
Inter-agency harmonized criteria for the selection of artemisinin-based antimalarials
Inter-agency harmonized criteria for the selection of artemisinin-based antimalarials
GFATMQAP
criteria
• Restricted annual joint
tender
1. WHO Treatment Guidelines2. PQ approved or SRA-registered 3. Dossier accepted by PQ or SRA4. GMP compliance after inspection by WHO PQ or SRA
• Dossier submission only to SRA
• Inclusion only in National Treatment Guidelines
• Evaluation of IPPQ: - registration information, - regulatory (licensing) situation, - finished product specifications and compliance with International Pharmacopoeia standards, - stability data (in Zone IV), - labeling information, - API characteristics and certification.
Review of efficacy
and safety
9 July 2009 4 |GLOBAL
MALARIA PROGRAMME
New GFATM QA policy and selection of finished pharmaceutical products
New GFATM QA policy and selection of finished pharmaceutical products
PRs may procure a FPP recommended
by the ERP
For ARVs, antimalarial and anti-TB FPPs
Number of FPPs WHO prequalified or SRA authorized
Number of FPPs WHO prequalified or SRA authorized
If 2 or more FPPs WHO prequalified or SRA authorized
If 1 or 0 FPPs WHO prequalified
or SRA authorized
PR has to procure one
of these FPPs
If product not available°
° Inability to supply sufficient quantity of product within 90 days from date of order
Courtesy of Dr Sophie Logez, The Global Fund Courtesy of Dr Sophie Logez, The Global Fund
9 July 2009 5 |GLOBAL
MALARIA PROGRAMME
Artemisinin-based antimalarial Medicines
on WHO/UNICEF procurement lists
(updated: 6.06.2009)
International Non-Proprietary
Name (INN) of productStrengthDosage formSupplier
Presentation
Packaging
Artemether / lumefantrine 20mg/120mgFixed dose
tabletsAjanta, India6x1 30 blisters / box
6x2 6x3 6x4 Cipla, India6x1 30 blisters / box 6x2 6x3 6x4 Ipca, India6x1 Single blisters 6x2 6x3 6x4
Novartis ,
6x1 30 blisters / box China/USA6x2 6x3 6x4
Artesunate + amodiaquine 25mg+67.5mg
Fixed dose tablets
Sanofi Aventis
325 blisters / box 50mg+135mg 100mg+270mg 100mg+270mg 6
50mg + 150mg
(base)Co-blistered
tabletsGuilin, China3+3 25 blisters / box
6+6 12+12
50mg + 153mg
(base)Co-blistered
tabletsCipla, India3+3 25 blisters / box
6+6 12+12
Ipca, India3+3 10 or 100 treatments / box
6+6 10 or 100 treatments / box
12+1210 or 100 treatments / box
Strides, India3+3 10 treatments / box 6+6 12+12
Artesunate + mefloquine 200mg + 250mgCo-blistered
tabletsMepha,
Switzerland 3+6Single blisters
Artesunate + 50mg + 500/25mg
Co-blistered tablets
Cipla, India 3+1 Single blisters
sulfadoxine/ pyrimethamine
6+2
12+3
Artemether20mg/mlInjectionDafra,
Belgium
3 3 Ampoules / pack
1010 Ampoules / pack 80mg/ml 5 5 Ampoules / pack
PrequalifiedPrequalified
9 July 2009 6 |GLOBAL
MALARIA PROGRAMME
Antimalarials recommended by ERP (with effect on 1.7.2009)
Antimalarials recommended by ERP (with effect on 1.7.2009)
Artemether/Lumefantrine
20mg/120mgTAB
Ipca Laboratories Ltd, Plot No. 255/1,
Village Athal, Dadra and Nagar
Haveli(U.T), Silvassa 396 230, India.
Al/PVC/PVDC blister(pack of 1x6's, 2x6's,
3x6's, 4x6's and 3x8's)
Artemether/Lumefantrine
40mg/240mgTAB
Cipla Limited, MIDC, Patalinga,
Plot A-33, -42 MIDC, Dist Raigad,
Maharashtra, India
Al/Al blister(pack of 3's, 6's and 12's)
Artesunate+ Sulphadoxine/
Pyramethine
50mg + (500 mg+25m
g)TAB
Cipla Limited, MIDC, Patalinga,
Plot A-33, -42 MIDC, Dist Raigad,
Maharashtra, India
CO BLISTER-PVC/PE/PVDC film
blister with (12 Art+ 3 SP tabs),
(6 Art+ 2 SP tabs),(3 Art+ 1SP
tab)
Quality Control of Pharmaceutical Products
Quality Control Test Multi Source
Single and limited
source products complying withoption A or B
Single and limited source products complying with
option C
ResponsibilityPR or sub recipientGF Secretariat
Condition (s)In accordance with the Good Procurement Practice
Notification submission by PR to GF No Objection by GF
WhenAfter receipt of drugs at country level
Before any shipment of
drugs to the country
FrequencyAt random, to be determined by the PR
Mandatory for all Purchase Order
LaboratoryTo be selected by PR, laboratory recognized by NDRA, WHO prequalified lab when possible
SGS laboratory , contracted by GF
Procedures and AssaysTo be defined by the PR and selected laboratory
Listed in SGS/GF Contract
All details in FAQ: http://www.theglobalfund.org/pdf/guidelines/QCTestingPharmaceuticalProducts.pdf
9 July 2009 8 |GLOBAL
MALARIA PROGRAMME
ACT Prices for procurement by WHO (last updated 15.01.2009)
ACT Prices for procurement by WHO (last updated 15.01.2009)
00.20.40.60.8
11.21.41.61.8
4
3
2
1
Pric
e pe
r uni
t tr
eatm
ent (
USD
)Pr
ice
per u
nit
trea
tmen
t (U
SD)
Age
-gro
ups
Age
-gro
ups
ALAL
AS+AQAS+AQASAQASAQ
AS+SPAS+SP
Fixed-Dose CombinationsFixed-Dose Combinations Co-blistered CombinationsCo-blistered Combinations
9 July 2009 9 |GLOBAL
MALARIA PROGRAMME
Adoption, deployment, past procurement and 2009 forecast of ACTs
Adoption, deployment, past procurement and 2009 forecast of ACTs
0.5 0.6 2.1 5
31.3
82.7
97
130
160
0
20
40
60
80
100
120
140
160
180
2001 2002 2003 2004 2005 2006 2007 2008 2009
0
10
20
30
40
50
60
70
80
90
ACT procured No countries: ACT 1st line No countries deploying
Mil
lio
ns
of
AC
T t
reat
men
t co
urs
es
Cu
mu
lati
ve n
um
ber
of
cou
ntr
ies
Forecast6-24 months from adoption to implementation6-24 months from adoption to implementation
9 July 2009 10 |GLOBAL
MALARIA PROGRAMME
Price reduction of artesunate + amodiaquine Price reduction of artesunate + amodiaquine over 6 UNICEF/WHO joint tenders over 6 UNICEF/WHO joint tenders
Price reduction of artesunate + amodiaquine Price reduction of artesunate + amodiaquine over 6 UNICEF/WHO joint tenders over 6 UNICEF/WHO joint tenders
0
0.5
1
1.5
2
2.5
2003 2004 2005 2006 2007 2008
Company A+X Company A Company B
Company C Company D Company E
Price per adult treatment course (USD)
Not
co-b
liste
red 14-38% 4-28%
10%5-10%0- 12%
9 July 2009 11 |GLOBAL
MALARIA PROGRAMME
Price reduction of Coartem® Price reduction of Coartem® (artemether-lumefantrine): 2003 - 2008(artemether-lumefantrine): 2003 - 2008
Price reduction of Coartem® Price reduction of Coartem® (artemether-lumefantrine): 2003 - 2008(artemether-lumefantrine): 2003 - 2008
0
0.5
1
1.5
2
2.5
2003 2004 2005 2006 2007 2008
6 x 1 tab 6 x 2 tabs 6 x 3 tabs 6 x 4 tabs
Price per adult treatment course (USD)
25 %22 %
9 July 2009 12 |GLOBAL
MALARIA PROGRAMME
Price variations relating to production and demand of artemisinin
Price variations relating to production and demand of artemisinin
Global shortageGlobal shortage
Relative over-supply Relative over-supply
USDUSDUSDUSD
Cost of production
Cost of production
0
200
400
600
800
1000
1200
2003 2004 2005 2006 2007 2008
Spot prices ofartemisininUSD/kg
9 July 2009 13 |GLOBAL
MALARIA PROGRAMME
Complex SCM of ACTs: example of AL Complex SCM of ACTs: example of AL
O
O
O
H3C
H
OO
H
H
O
O
H3C
H
OO
H
H
OH
O
OH
OO
H
H
OCH3
Artemisinin
Di-hydro-ArtemisininArtemether DS
Artemisia annua
1. Drying of leaves2. Extraction
3. Purrification
Yield: 0.3 - 0.5%
Seedling, nursery, plantation, growth and harvest (7 months) Seedling, nursery, plantation, growth and harvest (7 months)
Extraction
(1 month)
Extraction
(1 month)
Derivatisation (2 months)
Derivatisation (2 months)
Co-formulation, tabletting, packaging and shipping
(4 months)
Co-formulation, tabletting, packaging and shipping
(4 months)
GrowersGrowers API suppliersAPI suppliers
Manufacturersof finished pharmaceutical productsManufacturersof finished pharmaceutical products
Extractors
9 July 2009 14 |GLOBAL
MALARIA PROGRAMME
ACT demand and artemisinin supplyACT demand and artemisinin supply
Forecast of ACTs (in millions)
20092010
ACTs for public sector140190
ACTs for private sector through AMFm
1045
ACT in private sector105
total ACTs160240
Artemisinin forecast (in tonnes°)
80120
°2m treatments = 1 ton of artemisinin°2m treatments = 1 ton of artemisinin
Artemisinin supply(in tonnes)
200820092010
Secured for ACT production
80-9080-90
Requirements to meet ACT demand
80120
Artemisinin stocks available/gap
0-10-30-40
9 July 2009 15 |GLOBAL
MALARIA PROGRAMME
Revolving fund to artemisinin extractorsRevolving fund to artemisinin extractors
Triodos
Producer /exporter
Buyer /importer
(2) delivery ofproducts
(1) Loan (3) Payments amount X(4) Payments amounts X minus Y
Witholding of amount Y for repayment + interest
Artemisinin extractorsArtemisinin extractors API suppliers/ACT manucaturesAPI suppliers/ACT manucatures
Development BankDevelopment Bank
Malaria Diagnostics June 23 2009
Other Budget Categories $757M
PSM Costs $39M
Condoms, lubricant $23M
Reagents $33M
Test equipment (non-RDT:CD4, PCR, ELISA, etc.) $36M
Medicines for PEP $7M
Medicines for OI $24M
ARV2 $31M
ARV1 $134M
Other Budget Categories $502M
PSM Costs $133M
Other Health Products $3M
Microscopy $8M
IRS $36MRapid Diagnostic Test $45M
LLIN $749M
Other Anti-malarial Medicines $7M
ACT $86M
OtherBudget
Categories$210M
PSMCosts$13M
Othergenerallabequipment,supplies$17M
X-Rayequipment,film,consumables$20M
SecondLineAnti-TB$22M
FirstLineAnti-TB$19M
HIV Malaria TB
$1,164M $1,568M $327MTotal =$3,059M
0
20
40
60
80
100%
Malaria RDTs in context of overall Round 8 portfolio
Source: TRP Report on recommended proposals, sampling of detailed budgets for largest HIV and malaria grants, and procurement reported planned in proposal Attachment B’s.
Note that applicants were inconsistent in where freight, insurance, distribution, etc. costs were allocated. In most cases, it appears that these costs were included under “PSM Costs” but requires further review.
ESTIMATES
RDTs account for est. $45M or 3% of
R8 Malaria portfolio
Courtesy of Dr Joelle Daviaud, GFATMCourtesy of Dr Joelle Daviaud, GFATM
Malaria Diagnostics June 23 2009
Malaria RDTs in approved proposals for Rounds 6-8
Source: Sampling and analysis of proposal documents for R6-8.
ESTIMATES
Estimated Proposed RDT Procurement as Percentage of Total Malaria Budget in Approved Proposals by Round
6%4%
3%
0%
5%
10%
15%
20%
25%
6 7 8
Round
Estimated Proposed Malaria RDT Procurement included in Approved Proposals (Years 1-2) by Round
$12M
$20M
$45M
$0M
$10M
$20M
$30M
$40M
$50M
6 7 8
Round
• Significant increase in value of procurement proposed for malaria RDTs over Rounds 6-8• As percentage of total malaria proposal budgets, RDTs have accounted for 3-6% over last three rounds
• Significant increase in value of procurement proposed for malaria RDTs over Rounds 6-8• As percentage of total malaria proposal budgets, RDTs have accounted for 3-6% over last three rounds
Courtesy of Dr Joelle Daviaud, GFATM
Product lists and manufacturing qualitySubmission to Product Testing 2008
Access Bio ACON (Inverness) Alldiag Ameritek Amgenix AZOG Bhat biotec Binax (Inverness) BioMed Industries Bio-Quant Inc. Biosynex Biotech Laboratories Blue cross Bio Medical Brittney Ltd Cellabs Chemoquip Core Diagnostics Cortez CTK Dialab Diamed AG Fortress Diagnostics Genix technologies/Innovatek Guangzhou Wondfo Biotech GlobaleMed Hepatika Human Gmbh IND Intec International Immunodiagnostics J Mitra KAT Medical Makro Medical Merlin Labs Omega Diagnostics Orchid Biomedical Systems Pacific Biotec Premier Medical Corporation PT INneec R&R Marketing Sallamander Concepts Pvt Span Diagnostics Standard Diagnostics Syntillent Unimed Vision Biotech Zephyr Biomedical Systems Bio-Rad Bio Merieux SA Biotech Training partners Cumberland Diagnostics (Trinity Biotech PLC) Diazyme Genelabs Diagnotics Pvt Ltd
Access Bio ACON (Inverness) Alldiag Ameritek Amgenix AZOG Bhat Biotec Binax ((nverness) Biosynex Biotech Laboratories Cellabs Chemoquip Core Diagnostics Cortez Dialab Diamed AG Fortress Diagnostics Genix Technologies/Innovatek Guonzhou Wondfo Biotech Human Gmbh IND Intec Innovatek J Mitra Merlin Omega Diagnostics Orchid Biomedical Systems Premier Medical Corporation PT INdec R&R Marketing Span Diagnostics Standard Diagnostics Unimed Vision Biotech Zephyr Biomedical Systems
Access Bio, Inc. ACON Laboratories, Inc. Amgenix International, Inc. AZOG, Inc. Biosynex Diagnostics Automation Inc. DiaMed Human GmbH IND Diagnostic Inc. Innovatek Medical Inc. Intec Products Inc. Inverness Medical Innovations J. Mitra Company Pvt Ltd Orchid Biomedical Systems Premier Medical Corporation Ltd. ICT Diagnostics Span Diagnostics Standard Diagnostics, Inc. Unimed International, Inc. Vision Biotech Guangzhou Wondfo Biotech Co., Ltd Zephyr Biomedicals
ALL
60+ Manufacturers
~200 products
ISO13485:2003
35 Manufacturers
112 products
Evaluated 2008
21 Manufacturers
41 products
~ 60+ million tests procured in 2008
9 July 2009 20 |GLOBAL
MALARIA PROGRAMME
New Developments in 2007-2009: New Developments in 2007-2009:
The WHO Malaria RDT Evaluation Programme, jointly coordinated by WPRO, TDR, FIND and US CDC, completed Round 1 product testing in 2009 and publication of results allows comparative assessment of RDTs in relation to parasite detection thresholds, stability, false positivity rate, invalid test results and ease of use.
Product testing, together with pre/post-shipment lot-testing, allows informed decisions for procurement agencies to take place.
New WHO guidelines for Quality Assurance of Malaria Microscopy have been published and provide new and practical approaches for QA in malaria microscopy, including methods for accreditation of national expert microscopists, and routine validation of slide examination.
International QA systems in place
9 July 20099 July 2009
Product testing
2008
Pre-qualification
2010
Lot testing
2007
International Quality Assurance Systems for Malaria Rapid Diagnostic Tests
Dossier review and manufacturer inspections
2009
9 July 20099 July 2009
200 para/ul x22000 para/uL x1
x12
Negative x10Report in 5 wk days
Procurement
Release to field
200 para/ul x22000 para/uL x1
x6
Negative x2
Report every 3 months
125 RDTs
Country programme Lot-testing lab
Requirements:125 Pf RDTs175 Pf-pan RDTs
Failures:Follow re-testing algorithmConfirm at second lab
End of shelf life
Incubate
QC Lot-testing of Malaria RDTsQC Lot-testing of Malaria RDTs
Courtesy of Dr Jennifer Juchavez, RITMCourtesy of Dr Jennifer Juchavez, RITM
9 July 20099 July 2009
Summary of RDT lot testing performed at RITM (2003-07)
- 134 lots, from 27 manufacturers, >400 reports, 2-4 lots/month
TOTAL
QC Testing Result
Pass(%)
Deferred/Failed
Pf (%)
Non-Pf (%)
2003*62
(33.3)4
(66.7)0
(0.0)
20042518
(72.0)4
(16.0)3
(12.0)
20052919
(65.5)3
(10.3)7
(24.1)
20062624
(92.3)1
(3.8)1
(3.8)
20074844
(91.7)1
(2.1)3
(6.3)
TOTAL134107
(79.9)13
(9.7)14
(10.4)* Initial development of SOPs for QC lot testing.
Courtesy of Dr Jennifer Juchavez, RITMCourtesy of Dr Jennifer Juchavez, RITM
Phase 2 Detection Rate for P. falciparum samples
Fir
st
Re
sp
on
se
Ma
lari
a A
g C
om
bo
(P
LD
H/H
RP
2)
Fir
st
Re
sp
on
se
Ma
lari
a A
g H
RP
2
Ca
re
Sta
rt M
ala
ria
HR
P2
(P
f)
Ad
va
nta
ge
P.f
. M
ala
ria
Ca
rd
Ca
re
Sta
rt M
ala
ria
HR
P2
/pL
DH
(P
f/P
AN
) C
OM
BO
SD
BIO
LIN
E M
ala
ria
Ag
Pf
SD
BIO
LIN
E M
ala
ria
Ag
Pf/
Pa
n
Imm
un
oq
uic
k M
ala
ria
+4
Ca
re
Sta
rt M
ala
ria
pL
DH
(P
AN
)
Ma
lari
a P
las
mo
diu
m f
alc
ipa
ru
m R
ap
id t
es
t D
ev
ice
(W
ho
le b
loo
d)
Bin
ax
No
w
Ma
laria
Imm
un
oq
uic
k M
ala
ria
Fa
lcip
aru
m
Ma
lari
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ap
id C
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Ma
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Co
mb
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as
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st
(ML
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)
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Ma
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ss
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es
t (M
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Pa
rah
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D
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OR
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M M
AL
AR
IA
AZ
OG
Ma
lari
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/p
v (
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) A
nti
ge
n D
ete
cti
on
Te
st
De
vic
e
Ma
lari
a R
ap
id D
ua
l
Pa
rac
he
ck
Pf
Ra
pid
te
st
for
P.f
alc
ipa
rum
Ma
lari
a (
Dip
sti
ck
)
Ma
lari
a P
.F/V
iva
x
Ad
va
nta
ge
Pa
n M
ala
ria
Ca
rd
Ma
lari
a R
ap
id P
f
AD
VA
NC
ED
QU
AL
ITY
TM
On
e S
tep
Ma
lari
a (
p.f
.) T
es
t (w
ho
le b
loo
d)
Ma
las
ca
n R
ap
id T
es
t fo
r M
ala
ria
Pf/
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n (
De
vic
e)
Ad
va
nta
ge
Ma
l C
ard
Wo
nd
fo O
ne
Ste
p M
ala
ria
Pf/
Pa
n W
ho
le B
loo
d T
es
t
On
Sig
ht
– P
ara
Qu
ick
(P
an
AD
VA
NC
ED
QU
AL
ITY
TM
M
AL
AR
IA (
p.f
) P
OC
T
Pa
rac
he
ck
Pf
Ra
pid
te
st
for
P.
falc
ipa
ru
m M
ala
ria
( D
ev
ice
)
Pa
ras
cre
en
Ra
pid
Te
st
fo
r M
ala
ria
Pa
n/P
f (D
ev
ice
)
Fir
stS
ign
– P
ara
Vie
w-2
(P
v +
Pf)
Ca
rd T
es
t
He
xa
go
n M
ala
ria
Co
mb
i
He
xa
go
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ala
ria
Pa
rah
it-f
T
ES
T D
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R F
AL
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AR
UM
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tiM
AL
-IT
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l D
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ice
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pid
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st
for
P.
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rum
an
d P
an
ma
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l s
pe
cie
s.
Fir
stS
ign
– M
ala
ria
Pf
Ca
rd
Te
st
SD
BIO
LIN
E M
ala
ria
Ag
On
e S
tep
Ma
lari
a A
nti
ge
n S
trip
Pa
rab
an
k R
ap
id T
es
t fo
r M
ala
ria
Pa
n (
De
vic
e)
Qu
ick
sti
ck
Ma
laria
An
tig
en
Te
st
0
25
50
75
100
200 (HRP2)
200 (pLDH)
2000 (pLDH)
2000 (HRP2)
De
tec
tio
n r
ate
(%
)
Phase 2
P. vivax detection
P. vivax Detection Rate
Ad
va
nta
ge
Ma
l C
ard
Ad
va
nta
ge
Pa
n M
ala
ria
Ca
rdC
are
Sta
rt M
ala
ria
pL
DH
(P
AN
)O
pti
MA
L-I
TC
are
Sta
rt M
ala
ria
HR
P2
/pL
DH
(P
f/P
AN
) C
OM
BO
Fir
st
Re
sp
on
se
Ma
lari
a A
g C
om
bo
(P
LD
H/H
RP
2)
On
Sig
ht
– P
ara
Qu
ick
(P
an
Pf)
Te
st
SD
BIO
LIN
E M
ala
ria
Ag
SD
BIO
LIN
E M
ala
ria
Ag
Pf/
Pa
n
AZ
OG
Ma
lari
a p
f (H
RP
-II)
/p
v (
pL
DH
) A
nti
ge
n D
ete
cti
on
Te
st
De
vic
eIm
mu
no
qu
ick
Ma
lari
a +
4P
ara
ba
nk
Ra
pid
Te
st
for
Ma
lari
a P
an
(D
ev
ice
)W
on
dfo
On
e S
tep
Ma
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a P
f/P
an
Wh
ole
Blo
od
Te
st
Pa
ras
cre
en
Ra
pid
Te
st
fo
r M
ala
ria
Pa
n/P
f (D
ev
ice
)B
ina
x N
ow
M
ala
ria
M
ala
ria
Ra
pid
Co
mb
oM
ala
ria
Ra
pid
Du
al
Fir
stS
ign
– P
ara
Vie
w-2
(P
v +
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Ca
rd T
es
tH
ex
ag
on
Ma
lari
a C
om
bi
ICT
Ma
lari
a C
om
bo
Ca
ss
ett
e T
es
t (M
L0
2)
Ma
lari
a P
.F/V
iva
xM
ala
sc
an
Ra
pid
Te
st
for
Ma
lari
a P
f/P
an
(D
ev
ice
)O
ne
Ste
p M
ala
ria
An
tig
en
Str
ipP
ara
hit
-To
tal D
ev
ice
Ra
pid
te
st
for
P. fa
lcip
aru
m a
nd
Pa
n m
ala
ria
l s
pe
cie
s.
Qu
ick
sti
ck
Ma
lari
a A
nti
ge
n T
es
t
0
25
50
75
100
200 (aldolase)200 (pLDH)2000 (aldolase)2000 (pLDH)
Dete
cti
on
rate
(%
)
Phase 2 Detection Rate for P. falciparum samples
Fir
st
Re
sp
on
se
Ma
lari
a A
g C
om
bo
(P
LD
H/H
RP
2)
Fir
st
Re
sp
on
se
Ma
lari
a A
g H
RP
2
Ca
reS
tart
Ma
lari
a H
RP
2 (
Pf)
Ad
va
nta
ge
P.f
. M
ala
ria
Ca
rd
Ca
reS
tart
Ma
lari
a H
RP
2/p
LD
H (
Pf/
PA
N)
CO
MB
O
SD
BIO
LIN
E M
ala
ria
Ag
Pf
SD
BIO
LIN
E M
ala
ria
Ag
Pf/
Pa
n
Imm
un
oq
uic
k M
ala
ria
+4
Ca
reS
tart
Ma
lari
a p
LD
H (
PA
N)
Ma
lari
a P
las
mo
diu
m f
alc
ipa
rum
Ra
pid
te
st
De
vic
e (
Wh
ole
blo
od
)
Bin
ax
No
w
Ma
lari
a
Imm
un
oq
uic
k M
ala
ria
Fa
lcip
aru
m
Ma
lari
a R
ap
id C
om
bo
ICT
Ma
lari
a C
om
bo
Ca
ss
ett
e T
es
t (M
L0
2)
ICT
Ma
lari
a P
f C
as
se
tte
Te
st
(ML
01
)
Pa
rah
it-f
D
IPS
TIC
K F
OR
FA
LC
IPA
RU
M M
AL
AR
IA
AZ
OG
Ma
lari
a p
f (H
RP
-II)
/p
v (
pL
DH
) A
nti
ge
n D
ete
cti
on
Te
st
De
vic
e
Ma
lari
a R
ap
id D
ua
l
Pa
rac
he
ck
Pf
Ra
pid
te
st
for
P.f
alc
ipa
rum
Ma
lari
a (
Dip
sti
ck
)
Ma
lari
a P
.F/V
iva
x
Ad
va
nta
ge
Pa
n M
ala
ria
Ca
rd
Ma
lari
a R
ap
id P
f
AD
VA
NC
ED
QU
AL
ITY
TM
On
e S
tep
Ma
lari
a (
p.f
.) T
es
t (w
ho
le b
loo
d)
Ma
las
ca
n R
ap
id T
es
t fo
r M
ala
ria
Pf/
Pan
(D
ev
ice
)
Ad
va
nta
ge
Ma
l C
ard
Wo
nd
fo O
ne
Ste
p M
ala
ria
Pf/
Pa
n W
ho
le B
loo
d T
es
t
On
Sig
ht
– P
ara
Qu
ick
(P
an
AD
VA
NC
ED
QU
AL
ITY
TM
M
AL
AR
IA (
p.f
) P
OC
T
Pa
rac
he
ck
Pf
Ra
pid
te
st
for
P.
falc
ipa
rum
Ma
lari
a (
De
vic
e)
Pa
ras
cre
en
Ra
pid
Te
st
fo
r M
ala
ria
Pa
n/P
f (D
ev
ice
)
Fir
stS
ign
– P
ara
Vie
w-2
(P
v +
Pf)
Ca
rd T
es
t
He
xa
go
n M
ala
ria
Co
mb
i
He
xa
go
n M
ala
ria
Pa
rah
it-f
T
ES
T D
EV
ICE
FO
R F
AL
CIP
AR
UM
MA
LA
RIA
Op
tiM
AL
-IT
Pa
rah
it-T
ota
l D
ev
ice
Ra
pid
te
st
for
P.
falc
ipa
rum
an
d P
an
ma
lari
al
sp
ec
ies
.
Fir
stS
ign
– M
ala
ria
Pf
Ca
rd T
es
t
SD
BIO
LIN
E M
ala
ria
Ag
On
e S
tep
Ma
lari
a A
nti
ge
n S
trip
Pa
rab
an
k R
ap
id T
es
t fo
r M
ala
ria
Pa
n (
De
vic
e)
Qu
ick
sti
ck
Ma
lari
a A
nti
ge
n T
es
t
0
25
50
75
100
200 (HRP2)
200 (pLDH)
2000 (pLDH)
2000 (HRP2)
De
tec
tio
n r
ate
(%
)
P. vivax Detection Rate
Ad
va
nta
ge
Ma
l C
ard
Ad
va
nta
ge
Pa
n M
ala
ria
Ca
rd
Ca
re
Sta
rt M
ala
ria
pL
DH
(P
AN
)
Op
tiM
AL
-IT
Ca
re
Sta
rt M
ala
ria
HR
P2
/pL
DH
(P
f/P
AN
) C
OM
BO
Fir
st
Re
sp
on
se
Ma
laria
Ag
Co
mb
o (P
LD
H/H
RP
2)
On
Sig
ht
– P
ara
Qu
ick
(P
an
Pf)
Te
st
SD
BIO
LIN
E M
ala
ria
Ag
SD
BIO
LIN
E M
ala
ria
Ag
Pf/
Pa
n
AZ
OG
Ma
laria
pf
(HR
P-I
I) /p
v (
pL
DH
) A
nti
ge
n D
ete
cti
on
Te
st
De
vic
e
Imm
un
oq
uic
k M
ala
ria
+4
Pa
rab
an
k R
ap
id T
es
t fo
r M
ala
ria
Pa
n (
De
vic
e)
Wo
nd
fo O
ne
Ste
p M
ala
ria
Pf/
Pa
n W
ho
le B
loo
d T
es
t
Pa
ras
cre
en
Ra
pid
Te
st
fo
r M
ala
ria
Pa
n/P
f (D
ev
ice
)
Bin
ax
No
w M
ala
ria
Ma
laria
Ra
pid
Co
mb
o
Ma
laria
Ra
pid
Du
al
Fir
stS
ign
– P
ara
Vie
w-2
(P
v +
Pf)
Ca
rd
Te
st
He
xa
go
n M
ala
ria
Co
mb
i
ICT
Ma
laria
Co
mb
o C
as
se
tte
Te
st
(ML
02
)
Ma
laria
P.F
/Viv
ax
Ma
las
ca
n R
ap
id T
es
t fo
r M
ala
ria
Pf/
Pa
n (
De
vic
e)
On
e S
tep
Ma
laria
An
tig
en
Str
ip
Pa
rah
it-T
ota
l D
ev
ice
Ra
pid
te
st
for P
. fa
lcip
aru
m a
nd
Pa
n m
ala
ria
l s
pe
cie
s.
Qu
ick
sti
ck
Ma
laria
An
tig
en
Te
st
0
25
50
75
100
200 (aldolase)200 (pLDH)2000 (aldolase)2000 (pLDH)
Dete
cti
on
rate
(%
)
Combo tests with high detection rate of both P. falciparum and P. vivax at 200 parasites/µlCombo tests with high detection rate of both P. falciparum and P. vivax at 200 parasites/µl
WHO procurement criteria for malaria RDTs:
evolution over time Criteria for inclusion:
2006: ISO13485:2003 or ‘sufficient equivalence’ *
2007: ISO13485:2003 or US FDA 21 CFR 820 *
2008: Only Products submitted to WHO Product- Testing Programme
2009: RDTs with good performance in product testing
* Plus credible heat-stability protocol
9 July 2009 28 |GLOBAL
MALARIA PROGRAMME
Select RDTs with:– high detection rate, – low false positive
rate, – low invalid rate.
In populations with low immunity, higher detection of low parasitaemia is important
9 July 2009 29 |GLOBAL
MALARIA PROGRAMME
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
Pf-only
Combo
Pan-malariaPrice per test (USD)
n=3n=3
n=8n=8
n=10n=10
RDTs eligible for procurementby WHO and UNICEF
RDTs eligible for procurementby WHO and UNICEF
USDUSD
Current WHO/UNICEF prices of malaria RDTs eligible for RFP 2009-2010
Current WHO/UNICEF prices of malaria RDTs eligible for RFP 2009-2010
RDTs with highest detection at 200 parasites/µl
RDTs with highest detection at 200 parasites/µl