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Suggested use of terms, requirements and preferences for labelling and instructions for use
Malaria rapid diagnostic test products
Global Malaria Programme
© World Health Organization 2017
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Suggested citation. Malaria rapid diagnostic test products: Suggested use of terms, requirements and preferences for labelling and instructions for use. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
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WHO/HTM/GMP/2017.16
Table of contents
Introduction 1
Suggested use of terms 2
WHO requirements and preferences for the labelling of malaria RDT kit components: box, cassette packaging, cassette, buffer bottle and accessories 8
Labelling of the RDT box 9
Labelling of kit contents 12
Labelling of the cassette 14
Labelling of the buffer bottle 16
Labelling of accessories 17
WHO suggested generic template for Instructions for Use (IFU) 19
Annexes 32
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
1
InTRODUcTIOn
Rapid diagnostic tests (RDTs) largely account for the scale-up of malaria diagnosis in endemic settings. However, diversity in terminology, labelling and the instructions for use (IFU) limits their interchangeability and userfriendliness. Uniform, easy to follow and consistent terminology and labelling, aligned with international standards and appropriate for the level of the end user’s education and training, is crucial. This document is intended as a reference for malaria RDT manufacturers and follows on from the consensus building efforts of a 2014 Roll Back Malaria Partnership stakeholder consultation and special taskforce to harmonize terms and abbreviations as well as specifications for labelling of box, device packaging, cassettes, buffer bottle and accessories.1 Specifically, this reference indicates if WHO considers these specifications are requirements based on international standards or preferences based on the outcome of consultations with country programme implementers, experts in RDT implementation, IVD regulatory experts and manufacturers. These requirements and preferences are aligned with those of the WHO Prequalification (PQ) of IVDs programme and compliance will be monitored through the dossier and laboratory evaluation components of the WHO PQ process.2
1 Jacobs et al. Malaria Journal 2014, 13:505.2 http://www.who.int/malaria/publications/atoz/978924151268/en/
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
3
PReF
eRRe
D T
eRm
Ab
bRev
.D
eSc
RIPT
IOn
SynO
nym
(N
OT
SUG
GES
TED
TER
M)
cO
mm
enTS
cAT
egO
Ry
Acce
ssor
ies
Artic
les
inte
nded
and
val
idat
ed b
y th
e RD
T m
anuf
actu
rer
to b
e us
ed w
ith th
e RD
T in
ord
er to
ach
ieve
its
inte
nded
pu
rpos
e (i.
e. s
peci
men
tran
sfer
dev
ice,
lanc
et, a
lcoh
ol
swab
)
Anc
illar
y ite
ms
The
acce
ssor
ies
prov
ided
mig
ht b
e re
plac
ed b
y ot
her i
tem
s with
out c
ompr
omisi
ng s
afe,
acc
urat
e pe
rfor
man
ce o
f the
test
, e.g
. diff
eren
t lan
cets
This
poss
ibili
ty o
f sub
stitu
tion
diffe
rent
iate
s “a
cces
sorie
s”
from
“com
pone
nts”
(see
‘Com
pone
nt’).
Alco
hol s
wab
A pa
d sa
tura
ted
with
alc
ohol
that
is u
sed
to c
lean
and
/or
disin
fect
ski
nAl
coho
l pad
, alc
ohol
w
ipe,
alc
ohol
pre
-pad
Ther
e w
as c
onse
nsus
that
“alc
ohol
sw
ab” i
s th
e te
rm in
br
oade
st u
se, b
oth
in s
poke
n la
ngua
ge a
nd in
labe
lling
.
Buff
erA
buffe
red
solu
tion
to e
nabl
e sp
ecim
en fl
ow a
nd
cond
ition
ing
of s
peci
men
s, to
opt
imiz
e se
nsiti
vity
and
m
inim
ize
non-
spec
ific
reac
tions
.
Man
y sy
nony
ms
are
in u
se, e
.g. “
bloo
d ly
sis
buffe
r”, “c
lear
ing
buffe
r”,
“ass
ay d
iluen
t”, “s
ampl
e di
luen
t”, “r
eage
nt”
Buff
er b
ottle
Plas
tic b
ottle
, ofte
n w
ith c
ap a
nd n
ozzl
e, c
onta
inin
g th
e bu
ffer,
inte
nded
to b
e us
ed in
mul
tiple
test
s
Buff
er v
ial
Smal
l via
l con
tain
ing
a su
ffici
ent v
olum
e of
buff
er to
pe
rfor
m a
sin
gle
RDT
test
. See
“prim
ary
pack
agin
g”
“Buff
er a
mpu
lla”
Buff
er w
ell
Phys
ical
pla
ce in
the
test
dev
ice
in w
hich
the
buffe
r is
appl
ied.
Som
e RD
Ts h
ave
a sin
gle
wel
l for
bot
h bu
ffer a
nd s
peci
men
.
Cas
sett
eTh
is is
the
test
form
at in
whi
ch th
e ni
troce
llulo
se s
trip
is
enca
sed
in a
pla
stic
hou
sing,
pre
sent
ing
open
ings
for t
he
resu
lt w
indo
w, f
or th
e sp
ecim
en a
nd b
uffer
wel
l(s) a
nd in
so
me
case
s fo
r eva
pora
tion.
Com
mon
ly re
ferr
ed to
as
the
“dev
ice”
Com
bina
tion
rapi
d di
agno
stic
test
Test
for d
etec
ting
mul
tiple
mal
aria
spe
cies
and
whi
ch
dist
ingu
ishes
P. f
alci
paru
m fr
om o
ther
mal
aria
spe
cies
Com
mon
ly re
ferr
ed to
as
a “c
ombo
test
”
Com
pone
ntD
edic
ated
par
ts o
f a fi
nish
ed, p
acka
ged,
labe
lled
RDT
kit t
hat a
re s
peci
fic to
and
nec
essa
ry fo
r per
form
ing
the
RDT.
The
se in
clud
e th
e te
st d
evic
e, b
uffer
bot
tle/v
ial a
nd
inst
ruct
ions
for u
se.
Not
e: T
here
can
be
no s
ubst
itutio
n fo
r a k
it co
mpo
nent
, w
here
as a
cces
sorie
s su
ch a
s a
lanc
et o
r alc
ohol
sw
ab
may
be
repl
aced
by
item
s th
at p
erfo
rm th
e sa
me
func
tion
or a
re p
urch
ased
sep
arat
ely.
Con
trol
line
Visib
le li
ne o
n th
e ni
troce
llulo
se s
trip
that
gen
eral
ly o
nly,
in
dica
tes
satis
fact
ory
mig
ratio
n of
buff
er a
Des
icca
ntD
ryin
g ag
ent u
sed
to p
rote
ct th
e te
st d
evic
e fr
om
hum
idity
. The
se m
ay c
hang
e co
lour
(sel
f-in
dica
ting)
to
indi
cate
hum
idity
sat
urat
ion.
The
bea
ds a
re c
onta
ined
in
a tra
nspa
rent
, par
tially
tran
spar
ent o
r non
-tra
nspa
rent
fib
er p
ouch
.
Silic
a ge
l is
the
mos
t co
mm
only
use
d de
sicca
nt fo
r RD
T pr
oduc
ts.
4
PReF
eRRe
D T
eRm
Ab
bRev
.D
eSc
RIPT
IOn
SynO
nym
(N
OT
SUG
GES
TED
TER
M)
cO
mm
enTS
cAT
egO
Ry
In v
itro
diag
nost
ic
med
ical
dev
ice
A de
vice
, use
d al
one
or in
com
bina
tion,
inte
nded
by
the
man
ufac
ture
r for
in v
itro
exam
inat
ion
of s
peci
men
s de
rived
from
the
hum
an b
ody,
sol
ely
or p
rinci
pally
to
pro
vide
info
rmat
ion
for d
iagn
osis,
mon
itorin
g or
co
mpa
tibili
ty. T
hey
incl
ude
reag
ents
, cal
ibra
tors
, con
trol
mat
eria
ls, s
peci
men
rece
ptac
les,
softw
are,
rela
ted
inst
rum
ents
or a
ppar
atus
or o
ther
art
icle
s (In
tern
atio
nal
Med
ical
Dev
ices
Reg
ulat
ors
foru
m)
http
://w
ww
.imdr
f.org
/do
cs/g
htf/
arch
ived
/sg
1/te
chni
cal-
docs
/gh
tf-sg
1-n0
45r1
2-in
-vitr
o-di
agno
stic
-cl
assifi
catio
n-07
0209
.pd
f
Requ
ired
Inst
ruct
ions
for u
se
IFU
Info
rmat
ion
prov
ided
by
the
man
ufac
ture
r to
the
user
ab
out t
he in
tend
ed p
urpo
se a
nd p
rope
r use
of i
n vi
tro
diag
nost
ics
and
any
prec
autio
ns to
be
take
n (G
HTF
/SG
1/n7
0:20
11)
“Pac
kage
inse
rt”,
“inst
ruct
ions
leafl
et”
Requ
ired
Job
aid(
s)D
ocum
ent d
escr
ibin
g th
e es
sent
ial m
ater
ials
to p
erfo
rm
an R
DT
(i.e.
pro
cedu
re o
r int
erpr
etat
ion)
pro
vide
d ap
art
from
the
IFU,
eith
er a
s a
sepa
rate
leafl
et a
nd/o
r prin
ted
on th
e de
vice
pac
kagi
ng o
r in/
on th
e RD
T bo
x
“Qui
ck g
uide
”, “p
icto
gram
test
ing
proc
edur
e”
Refe
r to
the
“WH
O g
ener
ic jo
b ai
ds” f
or a
n ex
ampl
e.
Kit
Set o
f com
pone
nts
and
acce
ssor
ies
pack
ed to
geth
er
and
inte
nded
for u
sing
a sp
ecifi
c RD
T (te
st d
evic
e, b
uffer
bo
ttle,
spe
cim
en tr
ansf
er d
evic
e, la
ncet
, alc
ohol
sw
ab,
inst
ruct
ions
for u
se) (
defin
ition
ada
pted
from
ISO
18113
-1:2
009)
Requ
ired
Lanc
etSh
arp,
nee
dle-
like,
ste
rile
med
ical
dev
ice
used
to
punc
ture
ski
n to
obt
ain
bloo
d (C
LSI H
04-A
6)Th
ey in
clud
e:
•pl
ain
met
al la
ncet
s (p
acke
d in
a s
ingl
e pa
ckag
es fo
r st
erili
ty)
•sa
fety
-sea
l lan
cets
(in
plas
tic h
ousin
g w
ith a
pla
stic
cap
)•
auto
-lan
cing
lanc
ets
(mou
nted
in p
last
ic h
ousin
g th
at is
ej
ecte
d au
tom
atic
ally
whe
n th
e pl
unge
r is
pres
sed)
•au
to-r
etra
ctab
le la
ncet
s (m
ount
ed in
pla
stic
hou
sing
that
is re
tract
ed a
utom
atic
ally
afte
r pun
ctur
e)
Lot
Defi
ned
amou
nt o
f mat
eria
l with
uni
form
pro
pert
ies
that
ha
s be
en p
rodu
ced
in o
ne p
roce
ss o
r ser
ies
of p
roce
sses
so
that
it c
an b
e ex
pect
ed to
be
hom
ogen
eous
(ISO
18113
-1:2
009)
“Bat
ch”
Requ
ired
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
5
PReF
eRRe
D T
eRm
Ab
bRev
.D
eSc
RIPT
IOn
SynO
nym
(N
OT
SUG
GES
TED
TER
M)
cO
mm
enTS
cAT
egO
Ry
Lot n
umbe
rD
istin
ctiv
e se
t of n
umbe
rs a
nd/o
r let
ters
for a
kit
or
com
pone
nt th
at s
peci
fical
ly id
entifi
es a
lot a
nd p
erm
its
traci
ng o
f its
man
ufac
ture
, pac
kagi
ng, l
abel
ling
and
dist
ribut
ion
hist
ory
(ISO
18113
-1:2
009)
“Bat
ch n
umbe
r”, “b
atch
co
de”
Requ
ired
Mal
aria
rapi
d di
agno
stic
test
RD
TA
colle
ctio
n of
reag
ents
and
oth
er a
ssoc
iate
d m
ater
ials
for
in v
itro
diag
nost
ics,
inte
nded
to b
e us
ed fo
r the
qua
litat
ive
and/
or q
uant
itativ
e de
tect
ion
of a
ntig
ens
from
one
or
mor
e sp
ecie
s of
Pla
smod
ium
in a
clin
ical
spe
cim
en w
ithin
a
shor
t per
iod,
rela
tive
to s
tand
ard
labo
rato
ry te
stin
g pr
oced
ures
, typ
ical
ly b
y an
imm
unoc
hrom
atog
raph
ic te
st
met
hod
This
test
is c
omm
only
use
d in
the
labo
rato
ry o
r in
poin
t-of
-car
e an
alys
es.
Man
ufac
ture
rAn
y na
tura
l or l
egal
per
son
with
resp
onsib
ility
for d
esig
n an
d/or
man
ufac
ture
of a
med
ical
dev
ice
with
the
inte
ntio
n of
mak
ing
the
med
ical
dev
ice
avai
labl
e fo
r use
, und
er
his
or h
er n
ame,
whe
ther
the
med
ical
dev
ice
is de
signe
d an
d/or
man
ufac
ture
d by
that
per
son
him
- or
her
self
or o
n hi
s or
her
beh
alf b
y an
othe
r per
son(
s) (G
HTF
/SG
1/N
055:
20
09 D
efini
tions
of t
he te
rms
“man
ufac
ture
r”, “a
utho
rized
re
pres
enta
tive”
, “di
strib
utor
” and
“im
port
er”)
Plas
mod
ium
an
tigen
Antig
en b
pro
duce
d by
mal
aria
par
asite
s an
d de
tect
ed
with
RD
TsTa
rget
, mar
ker,
anal
yte
Plas
mod
ium
P
“P” i
s to
be
used
onl
y as
the
abbr
evia
tion
of th
e ge
nus
and
in c
ombi
natio
n w
ith th
e sp
ecie
s na
me
(e.g
. P.
oval
e) o
r as
part
of th
e ab
brev
iatio
ns “P
m, P
o, P
v, P
f an
d Pv
om”;
it sh
ould
not
be
used
alo
ne.
pan-
A gr
oup
of h
uman
Pla
smod
ium
spe
cies
: Pf,
Pv, P
o an
d Pm
Plas
mod
ium
fa
lcip
arum
PfPl
asm
odiu
m fa
lcip
arum
Plas
mod
ium
(or
para
site)
lact
ate
dehy
drog
enas
e
pLD
H
Plas
mod
ium
(or p
aras
ite) l
acta
te d
ehyd
roge
nase
In p
aper
s an
d do
cum
ents
, bot
h “p
aras
ite” a
nd
“Pla
smod
ium
” lac
tate
deh
ydro
gena
se a
re u
sed.
In th
e pr
esen
t con
text
and
doc
umen
ts (s
uch
as IF
U).
it w
ould
be
bet
ter t
o m
aint
ain
“Pla
smod
ium
”
Plas
mod
ium
m
alar
iae
PmPl
asm
odiu
m m
alar
iae
Plas
mod
ium
ova
lePo
Plas
mod
ium
ova
le
Plas
mod
ium
viv
axPv
Pl
asm
odiu
m v
ivax
6
PReF
eRRe
D T
eRm
Ab
bRev
.D
eSc
RIPT
IOn
SynO
nym
(N
OT
SUG
GES
TED
TER
M)
cO
mm
enTS
cAT
egO
Ry
Plas
mod
ium
viv
ax,
oval
e, m
alar
iae
Pvom
Plas
mod
ium
viv
ax, o
vale
, mal
aria
e
Poin
t-of
-car
e te
stin
g PO
CTTe
stin
g us
ed a
t or n
ear t
he s
ite o
f pat
ient
car
e, le
adin
g to
a
poss
ible
cha
nge
in th
e ca
re o
f the
pat
ient
(ISO
228
70
2006
)
Prim
ary
pack
agin
g of
alc
ohol
sw
abs,
lanc
ets,
desic
cant
an
d ca
sset
tes
Laye
r of p
acka
ging
in im
med
iate
con
tact
with
the
item
Al
coho
l sw
ab, l
ance
t, de
sicca
nt o
r cas
sette
pa
ckag
ing
Pack
agin
g of
alc
ohol
sw
ab, l
ance
t, de
sicca
nt
or c
asse
tte
Pouc
h, s
ache
t
Use
“prim
ary
pack
agin
g” in
tech
nica
l com
men
ts
for m
anuf
actu
rers
(for
inst
ance
whe
n de
scrib
ing
requ
irem
ents
for l
abel
ling)
, and
use
“pac
kagi
ng
of th
e al
coho
l sw
ab” o
r “al
coho
l sw
ab p
acka
ging
” w
hen
addr
essin
g us
ers
durin
g tra
inin
g an
d in
IFU
(for
in
stan
ce: “
open
the
cass
ette
pac
kagi
ng”)
.
Prod
uct
RDT
as c
urre
ntly
mar
kete
d an
d id
entifi
ed, w
ith a
ssig
ned
nam
e, p
rodu
ct c
ode
and
regu
lato
ry v
ersio
n
Prod
uct c
ode
Uniq
ue c
ode
iden
tifyi
ng o
ne p
rodu
ct (o
r pro
duct
var
iant
) w
ith a
n as
signe
d na
me
and
a re
gula
tory
ver
sion
Cata
logu
e nu
mbe
r, pr
oduc
t num
ber,
refe
renc
e nu
mbe
r
RDT
box
or B
oxPh
ysic
al b
ox, u
sual
ly m
ade
of c
ardb
oard
, in
whi
ch th
e ki
t co
nten
ts (c
ompo
nent
s an
d ac
cess
orie
s) a
re p
acke
dSe
cond
ary
pack
agin
g,
kit b
ox
Read
ing
lege
ndAc
rony
ms
or c
hara
cter
s in
the
resu
lt w
indo
w, r
efer
ring
to th
e co
ntro
l and
test
line
s. T
he c
hara
cter
s m
ay b
e em
boss
ed in
the
plas
tic h
ousin
g or
prin
ted
on it
. The
re
adin
g le
gend
can
be
on e
ither
sid
e of
the
resu
lt w
indo
w.
Read
ing
scal
e
(Min
imum
and
m
axim
um) r
eadi
ng
time
Inte
rval
dur
ing
whi
ch v
alid
resu
lts c
an b
e ob
tain
ed
Resu
lt w
indo
wO
peni
ng in
the
test
cas
sette
sho
win
g th
e ar
ea o
f the
str
ip
cont
aini
ng th
e co
ntro
l and
test
line
(s)
Read
ing
win
dow
Revi
sion
hist
ory
A ta
ble
in w
hich
am
endm
ents
are
reco
rded
eac
h tim
e a
new
ver
sion
of th
e IF
U is
issu
ed
Sing
le p
ack
Kit i
ndiv
idua
lly p
acke
d w
ith a
ll th
e co
nten
t req
uire
d fo
r the
pe
rfor
man
ce o
f one
test
Si
ngle
test
pac
k,
singl
e te
st, i
ndiv
idua
lly
pack
aged
test
Spec
ies
spp.
Spec
ies
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
7
PReF
eRRe
D T
eRm
Ab
bRev
.D
eSc
RIPT
IOn
SynO
nym
(N
OT
SUG
GES
TED
TER
M)
cO
mm
enTS
cAT
egO
Ry
Spec
imen
wel
lPh
ysic
al p
lace
in th
e te
st c
asse
tte o
r dip
stic
k to
whi
ch th
e sp
ecim
en is
app
lied
Som
e m
alar
ia R
DTs
ha
ve a
sin
gle
wel
l for
bo
th s
peci
men
and
bu
ffer.
Spec
imen
tran
sfer
de
vice
D
evic
e us
ed to
tran
sfer
blo
od (o
r pla
sma
or s
erum
) to
the
test
dev
ice.
Thi
s in
clud
es: i
nver
ted
cup,
loop
, (gl
ass)
ca
pilla
ry tu
be, (
plas
tic) s
traw
, pip
ette
.
Sam
plin
g de
vice
The
term
“spe
cim
en tr
ansf
er d
evic
e” m
ay b
e sh
orte
ned
to “t
rans
fer d
evic
e”.
Sym
bol k
eyLi
st o
f sym
bols
with
writ
ten
expl
anat
ion
(“le
gend
”)Ke
y to
sym
bols
Test
line
Line
on
the
nitro
cellu
lose
str
ip th
at is
inte
nded
to d
ispla
y th
e re
actio
n w
ith a
spe
cific
targ
et a
ntig
en (H
RP2,
pLD
H,
aldo
lase
)
The
term
“ban
d” c
an
be u
sed
depe
ndin
g on
th
e RD
T de
sign
(two-
, th
ree-
and
four
-ban
d RD
T pr
oduc
ts)
Test
str
ipTh
e ph
ysic
al m
ediu
m, e
.g. n
itroc
ellu
lose
, in
whi
ch th
e m
igra
tion
and
reac
tion
take
pla
ce
“Tes
t mem
bran
e”
Two-
, thr
ee-
and
four
-ban
d RD
TsRD
Ts w
ith tw
o, th
ree
or fo
ur li
nes,
incl
udin
g th
e m
igra
tion
cont
rol l
ine,
and
one
, tw
o or
thre
e te
st li
nes
User
A
train
ed o
r ski
lled
pers
on, w
ho is
com
pete
nt a
nd w
ho
uses
the
RDT
Ope
rato
r, en
d-us
er
Vers
ion
num
ber
Num
ber g
iven
to a
ny la
belli
ng, i
nclu
ding
labe
ls,
inst
ruct
ions
for u
se (o
r job
aid
s) o
r any
oth
er m
ater
ials
dist
ribut
ed w
ith th
e pr
oduc
t, to
allo
w tr
acki
ng o
f cha
nges
.
a . I
n th
e ca
se o
f mal
aria
RD
Ts, t
he c
ontro
l lin
e be
com
es v
isibl
e if
suffi
cien
t dye
-lab
elle
d an
tibod
y (c
arrie
d in
the
buffe
r) a
ccum
ulat
es o
n th
e te
st s
trip
line
con
tain
ing
suffi
cien
t, in
tact
bou
nd
capt
ure
antib
ody.
b . A
ntig
ens
are
not r
ecom
bina
nt.
8
GeneRAL nOTe On LABeLLInG LeGIBILITy
There are no international guidelines on font sizes for labels of in-vitro diagnostics.
• According to the Guideline on the readability of the labelling and package leaflet of medicinal products for human use, revision 1, 12 January 2009, characters of at least 7 points (or of a size in which the lower case “x” is at least 1.4 mm in height) with a space between the lines of at least 3 mm are recommended.*
• The US Food and Drug Administration document Guidance on medical device patient labelling; final guidance for industry and FDA reviewers (2001), for patients and lay caregivers, recommends use of at least 12-point type whenever possible and a serif font for text.
* http://ec.europa.eu/health/files/eudralex/vol2/c/2009_01_12_readability_guideline_final_en.pdf
WHO requirements and preferences for the labelling of malaria RDT kit components
bOx, cASSeTTe PAckAgIng, cASSeTTe, bUFFeR bOTTle AnD AcceSSORIeS
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
9
labelling of the RDT box
Orientation
FIGURE 1. convention of terms for the front view of a malaria RDT box
labelling of the RDT box
• Left (lateral) • Front• Top • Right (lateral)• Back • Bottom
LefT (LATeRAL)
TOP
fROnT
RIGHT (LATeRAL)
BOTTOm
BACK
GeneRAL RequIRemenTS AnD PRefeRReD OPTIOnS fOR LABeLLInG mALARIA RDT BOxeS cATegORy
1. Labels should be printed on the cardboard as permanent printing or applied as water-resistant labels (applied with water-resistant glue). Printing should be indelible and should last the life span of the RDT product.
Preferred
2. use only internationally recognized symbols (ISO 15223–2012 or, if applicable, the Globally harmonized system of classification and labelling of chemicals.1
Required
3. Labelling must be legible, for instance in open letter type and font size equivalent to Miriad bold 10.
Required
4. The official language(s) in which the intended use is displayed should be relevant to the region in which the RDT product will be used. In Figure 2, English, French, Spanish and Portuguese are displayed.
Preferred
5. Display the essential information on the top (see Figure 2), front and at least one lateral side of the RDT box (left or right) (see Figure 3). The label contains all the relevant information required for stock management (e.g. product identity, storage conditions and material provided). An exception can be made for custom or variable prints, such as lot number and expiration date, and, in case of use, also production date. These can be printed on only one side of the box.
Preferred
1. http://www.hse.gov.uk/chemical-classification/labelling-packaging/hazard-symbols-hazard-pictograms.htm
10
What should be displayed: cATegORy
1. Product name with sufficient detail for the user to uniquely identify the device and its intended use, e.g.
• commercial name of the RDT product
• “malaria”
• targeted species and antigen(s)
• “antigen” or “Ag”
Required
2. Product code (and symbol) Required
3. Intended use (to be included if the product name does not include sufficiently specific information). If there is insufficient space on the label, this statement can be included on the IFU: diagnosis of malaria, in vitro diagnostic, professional use.
Required
4. number of tests provided in the kit box Required
5. In vitro diagnostic (symbol) Required
6. Name and physical address of the legal manufacturerTelephone and/or fax number and/or website
Required
7. Lot number (and symbol) Required
8. expiration date (and symbol)
Preferred format: YYYY-MM
Required
9.
9a.
9b.
materials (content) and quantities
• Materials provided, and quantities of each
• Items required but not provided, i.e. those items required for safe, accurate use of the test, such as a lancet (with symbol)
Required
Preferred
10. Storage conditions (symbols) Required
11. Warnings or precautions (symbols)
For instance: - do not use if package is damaged (symbol)
• read instructions before use (symbol)
• biohazard (symbol), if applicable i.e. desiccant containing cobalt chloride; buffer with sodium azide concentration (≥0.1%)
Required
12. Additional easily visible warning in case the procedure or Ifu has changed substantially
Information about the change and effective date should be included as a separate note in the box or in the IFU
Preferred
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
11
FIGURE 2. example label on the top of the RDT box. blue indicates specific RDT product items
4°C
30°C
commercial name, malaria Antigen Pf/Pan (HRP2/ pLDH) RDT
xxxxxxxxxx Σ
xx
Rapid test for the antigen detection of malaria (Plasmodium x)
Test rapide de détection d’antigène du paludisme (Plasmodium x)
Prueba rápida para detección de antígeno de malaria (Plasmodium x)
Teste rápido para detecção de antígeno da malária (Plasmodium x)
Professional use only
xxxxxxx
yyyy-mm
name, physical address of legal manufacturer, website, telephone and/or fax number
FIGURE 3. example labelling of one lateral side and the front of an RDT box. blue indicates specific RDT product items
commercial name, malaria Antigen Pf/Pan (HRP2/pLDH) RDT
xxxxxxxxxxx
Content: XX indicates quantities. Could state number of pouches and what each pouch contains
•Cassettes (xx)•Specimen•Transfer devices (xx)•Alcohol swabs (xx)•Lancets (xx)•Buffer bottle (xx)•Instructions for use (x)
Σxx
xxxxxxx
Indicate symbol for method of sterilization
Required but not provided
•Gloves•Biosafety sharps container•Biohazard waste container•Timer•Pencil/pen
yyyy-mm
4°C
30°C
12
labelling of kit contents
LABeLLInG Of CASSeTTe PRImARy PACKAGInG
What should be displayed: CATeGORy
1. Product name with sufficient detail for the user to uniquely identify the product and its intended use, e.g.
• commercial name of the RDT product
• “malaria”
• targeted species and antigen(s)
• “antigen” or “Ag”
Example: Commercial name, Malaria Pf/Pv (HRP2/pLDH) Antigen (RDT)
Required
2. for product code (or symbol) Preferred
3. Intended use (to be included if the product name does not include sufficiently specific information): If there is insufficient space on the label, this statement can be included on the IFU: diagnosis of malaria, in vitro diagnostic, professional use only, point-of-care.
Required
4. In vitro diagnostic (symbol) Required
5. name (or logo) of the legal manufacturer Required
6a.
6b.
Lot number (and symbol)
The lot number is preferably identical to the one on the RDT box.
Required
Preferred
7a.
7b.
expiration date (and symbol)
Preferred format: YYYY-MM
The expiration date is preferably identical to that on the RDT box. The expiration date must not be earlier than the expiration date on the RDT box.
Required
Preferred
8. quantity of tests per packaging (if more than one test) Preferred
9. unless there is no space, list contents of packaging and quantities, including desiccant
Preferred
10. Storage conditions (symbols) Required
11. Warnings or precautions (symbols)
For instance:
• do not use if package is damaged (symbol)
• read instructions before use (symbol)
• single use (symbol)
Required
GeneRAL nOTe
According to ISO 18113-2:2009, in the case of a kit, each component shall be identified by name, letter, number, symbol, colour or graphics in the same manner on all labels and in the instructions for use.
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
13
Where labels should be put:
Display all standard generic information on one side of the packaging and the custom or variable information (expiration date, lot number) on the opposite side. Preferred
FIGURE 4.example labelling of cassette primary packaging. blue indicates specific RDT product items
4°C
30°C
Commercial name, malaria Antigen Pf/Pan (HRP2/ pLDH) RDT
for product code: xxxxxxx
Σ xx
Content:• 1 cassette• 1 desiccant • 1 specimen transfer device
manufacturer name or logo
xxxxxxx
yyyy-mm
14
LefT
DISTAL
RIGHT
PROxImAL
Long
axi
s
Short axis
labelling of the cassette
convention of terms used to describe the orientation of the cassette
Figure 5 shows the most common RDT, a three-band RDT targeting two antigens (P. falciparum and pan-Plasmodium antigens) in a two-step procedure (add specimen, next add buffer), with a cassette containing individual specimen and buffer wells. The following convention of terms is used: proximal (closest to the specimen and buffer wells) and distal (at the end of the migration [absorption] pad). A vertical view of the cassette (with the direction of the specimen and buffer flow “upwards”) shows a right- and a left-hand side.
FIGURE 5.conventions for terms to describe the cassette
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
15
LABeLLInG: CATeGORy
1. Printing in indelible ink is recommended instead of characters embossed in the cassette housing. The test and control line legends and the actual test lines should be well aligned.
Preferred
2. All printing should be along the short axis. Preferred
3. A single, unequivocal reading legend should be present on the right-hand side of the results window.
Preferred
4. All abbreviations comply with those listed in document “Abbreviations”. In addition, “1” for the sample well, “2” for the buffer well (chronological order)
Preferred
5. Labelling must be legible: for instance, open letter type, clear print Required
note: The cassette surface should be of a material (and profile) on which it is possible to write (with a standard ink pen or pencil). Space should be left for writing patient identification. Preferred
What should be displayed: cATegORy
1. Product name (with indication of “Malaria”, antigen-based “Ag”, the Plasmodium species and the antigens detected) or logical abbreviation (referenced in the IFU)
Required
2. Labelled specimen and buffer wells (see above) e.g. “1” for the sample well, “2” for the buffer well (chronological order) – Preferred
Required
3. Reading legend with Plasmodium species detected (see abbreviations: Pf, pan, Pv)
Preferred
16
labelling of the buffer bottle
geneRAl ReqUIRemenTS AnD OUTlIneS FOR lAbellIng RDT bUFFeR bOTTleS: cATegORy
1. Labels: Well-fixed water-resistant label (applied with water-resistant glue) or permanent printing, indelible ink lasting the life span of the RDT product.
Preferred
2. use only internationally recognized symbols (ISO 15223–2012). Required
3. The official language(s) displayed should be relevant to the region in which the RDT product will be used.
Preferred
What should be displayed: cATegORy
1. Product name, with sufficient detail for the user to uniquely identify the product and its intended use, e.g.
• commercial name of the RDT product
• “malaria”
• targeted species and antigen(s)
• “antigen” or “Ag”
Example: Commercial name, Malaria Pf/Pv (HRP2/pLDH) Antigen(RDT)
(preferred option)
or with sufficient detail for the user to identify the type of product with which to use the buffer, e.g. Malaria RDT
(acceptable option)
Preferred
2. Contents: Buffer Required
3a.
3b.
For product code (symbol)
(preferred option)
or a reference code that is also written on the RDT packaging and/or in the instructions for use
(acceptable option)
Preferred
Required
4. In vitro diagnostic (symbol) Required
5. name (or logo) of the legal manufacturer Required
6. Lot number (and symbol) Required
7. Volume of contents or number of examinations that can be performed Required
8. expiration date (and symbol)
Preferred format: YYYY-MM
The expiration date must not be earlier than the expiration date on the RDT box and test packaging.
Required
Required
9. Storage conditions (symbols) Required
10. Warnings or precautions (symbols)
At least :do not use if package is damaged (symbol); hazard symbol, if sodium azide concentration is ≥ 0.1% (symbol); read instructions before use (symbol)
Required
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
17
FIGURE 6.Proposal for printing relevant information on the buffer bottle
4°C
30°C
Commercial name, malaria Antigen Pf/Pan (HRP2/ pLDH) RDT
for product code: xxxxxx
Contents : Buffer
xxxxxxx
yyyy-mm
manufacturer name (or logo)
xx ml or number of examinations
labelling of accessories
Definitions
Accessories of in vitro diagnostics are articles specifically and explicitly intended by the manufacturer to be used with a device to enable that device to be used in accordance with the intended purpose (ISO 18113-1, CE Directive 98/79). Specimen transfer devices, lancets, alcohol swabs and desiccant are included.
geneRAl ReqUIRemenTS AnD OUTlIneS: cATegORy
1. Labels should be printed on the device or packaging as permanent printing or applied as water-resistant labels (with water-resistant glue). The ink should be indelible and should last the life span of the product. If it is not practicable to display the information on the device itself (e.g. lancets, specimen transfer devices), some or all of the information may appear on the packaging of multiple items (if used) (GHTF/SG1/N70/2011:5.0 and Annex 1.8.8.1 of EU Directive 98/79).
Required
2. use of symbols, when adequate, is encouraged instead of text. Only Internationally recognized symbols (ISO 15223-2012) should be used.
Required
3. The language(s) used should be relevant to the region in which the RDT product will be used.
Preferred
4. The table below lists the information to be displayed on different accessories or on their packaging.
18
lAbel InFORmATIOn TRAnSFeR DevIce
lAnceT AlcOHOl SWAb
DeSIccAnT cATegORy
Name of accessory X X X X Required
Intended use if name of accessory does not indicate it (sufficient to identify the device and its intended use: e.g. transfer device, antiseptic, desiccant)
X X X X Required
Name of the legal manufacturer of the accessory (preferred to RDT manufacturer)
X X X X Preferred
For alcohol swab: antiseptic, product and concentration (e.g. isopropyl alcohol70%)
X Required
Product code of the accessory X X Preferred
For a transfer device other than inverted cup and loop: permanent volume mark
X Preferred
Lot number X X X Required
X Preferred
Indicate “in vitro diagnostic” use X
Expiration date (preferred format: YYYY-MM)
X Preferred
X X Required
Quantity of items, indicated on the outer packaging (if applicable) (symbol)
X X X Required
Specimen volume transferred X Preferred
Single use (symbol) X X X Required
Sterile (and by what method), if applicable
X Required
X Preferred
Do not use if package is damaged (symbol)
X X Required
Warning: “Do not swallow or eat” and “harmful” (text or symbols) in relevant language(s)
X Preferred
X Required
Interpretation of colour change, if applicable
X Required, if
applicable
Mal
aria
rap
id d
iag
nost
ic t
est
pro
duc
ts
sug
ges
ted
use
of
term
s, r
equ
irem
ents
an
d p
refe
ren
ces
for
labe
llin
g a
nd
inst
ruct
ion
s fo
r u
se
19
The present document is a template for generic IFU of malaria rapid diagnostic tests.
It must be adapted to the specific product.
Words or terms that are definitely product-related and variable are in blue. This template can be adapted according to present or future characteristics of the concrete product. Instructions for the designer are printed in italics and put into text boxes.
The present document uses the safety-seal lancet and inverted cup as an example. Other combinations are possible.
general suggestions
• Provide IFU version number including indication of language and date.
• Highlight changes (shaded in grey) with regard to the previous version.
• Text: ensure that the IFU is easily readable (e.g. Flesch-Kincaid grade < 6)
• use type size of at least 9 points, as measured in font ‘Times New Roman’, not narrowed, with a space between lines of at least 3 mm and an open letter type;
• use short sentences and terms that are easy to understand;
• use consistent terms and words throughout the IFU (see the section on Suggested use of terms);
• use active verb (imperative) rather than passive voice/”should”;
• stress important information (capitals, italics, underline);
• turn any list into a bulleted or numbered list;
• put “when” and “if” before “what” (“If the color indicator is red, discard the test”);
• put the warning before the action step in the procedure;
• make sure warnings are clearly indicated;
• use one line per action.
References on readability and a readability calculator are included in Annex 1.
• Figures:
• use figures that are large enough so that they are easily visible;
• drawings may be more informative than photographs;
WHO suggested generic template for Instructions for Use (IFU)
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• Generic job aids for malaria RDTs published by WHO-FIND provide clear drawings (see http://www.who.int/malaria/areas/diagnosis/rapid-diagnostic-tests/job-aids/en/);
• put figures on the left side, text on the right side;
• refer to each figure in the text;
• check that the figures match the real-life situation (device, transfer device, gloves, right-handed operator).
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TAble OF cOnTenTS
Product
• Product name
• Product code
• Number of tests provided in the kit
Intended use
• Test principle
• Intended user
• Required specimen
Warnings and precautions
materials
• Materials provided
• Materials required but not provided
Storage and stability
Procedure
• Before testing
• Sample preparation
• Test procedure
• Capillary whole blood from finger prick
• Venous whole blood from venipuncture
• Interpretation of the test result
limitations of the test, causes of false-negative and false-positive results
• Limitations of Malaria RDTs
• False negative results
• False positive results
• Invalid tests and problems of background clearing
Performance specifications
bibliography
manufacturer contact information
IFU version number and date of issue of the instructions for use
Symbol key
Product specific and other variables printed in blue
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Product
• Commercial name, Malaria Antigen Pf/Pan (HRP2/ pLDH) Rapid Diagnostic Test (RDT)
• Product code xxxxxx and presentation (number of tests per kit)
Intended use
This XXX test kit is an in-vitro diagnostic immunochromatographic assay for the qualitative detection of infection with Plasmodium parasites causing malaria in human whole blood specimens. It does not assess parasite densities.
It assists trained competent users and is not intended for lay users:
• in detecting Plasmodium infections
• to differentiate infection by Plasmodium falciparum from the non-P. falciparum species (Plasmodium vivax, Plasmodium malariae, Plasmodium ovale).
note: Malaria RDTs can give positive results after successful anti-malarial treatment. Therefore, the XXX test kit is not recommended for monitoring response to anti-malarial treatment.
Test principle
The following Plasmodium antigens are detected in this test:
• Histidine rich protein 2 specific for P. falciparum (Pf-HRP2)
• Plasmodium lactate dehydrogenase specific for P. falciparum (Pf-pLDH)
• Plasmodium lactate dehydrogenase specific for P. vivax (Pv-pLDH)
• Plasmodium lactate dehydrogenase common to all human Plasmodium species (pan-pLDH)
• Aldolase common to all human Plasmodium species
The cassette contains a test strip pre-coated with capture antibodies.
The sequence of events is as follows:
1. Whole blood is applied to the specimen well (labelled well 1).
2. Next, buffer is applied to the buffer well (labelled well 2).
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3. Migration of the specimen/buffer mixture starts, towards the other end of the cassette.
4. The specimen-buffer mixture passes the conjugate pad, which contains detection antibodies targeting Pf-HRP2, Pf-pLDH, Pv-pLDH, pan-pLDH and/or aldolase antigens. These detection antibodies are conjugated to colloidal gold. If present in the specimen, Plasmodium target antigens bind to this detection antibody-conjugate.
5. The antigen-antibody-conjugate complex migrates further and binds to the capture Plasmodium-specific antibodies present on the test line. These capture antibodies bind to another site (epitope) of the Plasmodium target antigens.
6. The capture antibodies are applied on a narrow section of the test strip: as a result, the antibody-conjugate with the colloidal gold will be concentrated and become visible as a red colored line.
7. The excess of the detection antibody-conjugate that was not bound by the Plasmodium target antigens and the capture antibodies moves further until it binds to a goat anti-mouse control antibody. There, the colloidal gold will create a red colored control line. The visualization of the control line indicates that the migration was successful. It does not confirm the presence of specimen.
The main components of the test are:
• Test strip:
• Detection antibodies conjugated to colloidal gold (in the conjugate pad):
– Mouse monoclonal antibodies (IgG) specific to Pf-HRP2-gold colloid
– Mouse monoclonal antibodies (IgG) specific to pan-pLDH-gold colloid
– (any other combination)
• Capture antibodies (on the nitrocellulose membrane):
– Plasmodium falciparum line: Mouse monoclonal antibodies (IgG) specific to Pf-HRP2
– Plasmodium species (pan) line: Mouse monoclonal antibodies (IgG) specific to pan-pLDH
• Control line (on the nitrocellulose membrane) : Goat anti-mouse polyclonal antibodies (IgG)
• Buffer vial:
• Bovine serum albumin, Triton X-100, Sodium azide (0.095 %)
Intended user
• The test is intended to be performed by a trained user.
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Specimen required
• Capillary whole blood or venous whole blood with the following anticoagulant: EDTA, heparin, oxalate or citrate.
• Time between specimen collection and specimen testing:
• Capillary: immediately
• Venous: immediately. If immediate testing is not possible, store the whole blood specimen at X-X °C for maximum XX hours.
Warnings and precautions
• For in vitro diagnostic use only.
• Read the instructions carefully before performing the test.
• Apply standard biosafety precautions for handling and disposal of potentially infective material.
• Handle all specimens as potentially infectious.
• Wear gloves while handling specimens and performing the test.
• Avoid splashing and aerosol formation.
• Clean up spills thoroughly using an appropriate disinfectant.
• The buffer contains 0.095% sodium azide as a preservative which may be toxic if ingested. When disposed of through a sink, flush with large quantities of water.
• Do not use any other buffer than the buffer supplied within this kit.
• Do not use the kit beyond the expiration date.
• Do not use if the packaging is damaged.
• Do not use any other specimen than whole blood.
• Do not use if the product has been exposed to excessive heat or humidity.
• Perform the test immediately after opening of the cassette packaging.
• Do not re-use the test.
materials
materials provided
• XX cassette package, each containing:
• 1 test device
• 1 packet of desiccant
• X buffer bottle(s) – XX ml
Do not use any other specimen than whole blood
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• XX specimen transfer devices (inverted cup) – x µl
• XX single-use safety-seal lancets
• XX alcohol swabs
• 1 instructions for use
materials required but not provided
• New pair of disposable gloves
• Pen/pencil
• Timer
• Extra lancets and alcohol swabs, if needed (lancet misfires, lancet does not produce sufficient blood volume, alcohol swab is dried out, etc.)
• Biosafety sharps container
• Biohazard waste container (for potentially infectious waste)
• If whole blood is collected by venipuncture, venipuncture blood collection materials and precision pipette, plus tips
Test kit storage and stability
• Store the kit between X–XX °C.
• Do not store the kit in the freezer.
• Protect the kit from humidity.
• The kit has a shelf life of XX months from the date of manufacture. The kit is stable until the expiration date marked on the RDT box and/or the packaging of individual components when stored as specified.
• The buffer is stable for XX months (or until the expiry date) even after opening.
Procedure
before testing
1. Prepare all necessary materials :
• When stored in the refrigerator, bring the kit to room temperature (XX-XX°C) minimum xx minutes before use.
• Prepare the materials (refer to the section on Materials).
2. Check the expiration date of the kit (including buffer).
If expired, do not use but take another unexpired kit.
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3. Check that the cassette packaging is not damaged.
If damaged, discard the test and use another test.
4. Open the cassette packaging and check the desiccant (if provided).
If there is a humidity indicator and it shows saturation (color changed from orange to green), throw away the cassette and take another cassette packaging.
If the color of the desiccant does not show a change, you can use the test.
Throw away the desiccant in the non-sharps (non-infectious) disposal container.
5. Take the cassette and place it on a flat surface, horizontally.
You see:
• a result window (marked with C, pan, Pf )
• a circle well marked “1” (for specimen)
• a square well “2” (for buffer)
6. Write the patient name or identifier on the cassette.
7. Put on gloves. Use new gloves for each patient.
8. Add if needed additional instructions on how to open the buffer bottle correctly – for instance, how to pierce the nozzle.
Test procedure (see reference Generic RDT training manual in Annex 2)
Capillary whole blood from finger prick
1. Wear gloves.
2. Choose a finger for the finger prick:
• Do not choose a finger that is swollen, bruised or scarred.
• Preferably choose the 3rd or 4th finger of the hand the patient does not use to write. Alternatively choose the heel or the earlobe for neonates.
3. Open the packaging of the alcohol swab. Take out the alcohol swab. Do not throw away the empty packaging (wrapper) but keep it aside.
4. Wipe the complete fingertip with the alcohol swab.
Wait until the finger has completely dried (minimum 30 seconds).
5. Place the alcohol swab in the wrapper and set it aside (you will use it again to stop the bleeding after you collected the patient’s blood).
6. Take the safety-seal lancet.
7. Detach the cap of the lancet.
Perform the test immediately after opening of the cassette packaging.
Do not re-use the test.
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Puncture the side of the pulp (ball) of the finger with the lancet, perpendicular to the lines of the fingerprint.
Dispose the lancet immediately into the sharps box.
8. Make sure a well-formed drop of blood is present.
9. If there is no well-formed drop of blood, repeat the finger prick using a new lancet and choose a different puncture site.
10. Take the inverted cup and collect 5 µl of blood by dipping the circular end of the inverted cup into the whole blood drop.
11. Place the circular end of the inverted cup in the circle well (marked “1”) so that it touches the strip (pad at the bottom of the well).
Press down lightly to transfer all the blood to the strip.
Put the used inverted cup into the non-sharps disposal container for potentially infectious waste.
12. Take the alcohol swab you put aside (step 5).
Ask the patient to press it to the finger prick to stop the bleeding.
After use, put the alcohol swab into the non-sharps disposal container for potentially infectious waste.
13. Take the buffer bottle.
Hold the open buffer bottle vertically above the square well (marked “2”).
In a vertical position, squeeze the buffer bottle gently and apply exactly X drops into the square well (marked “2”).
14. Remove your gloves and discard them into the non-sharps disposal container for potentially infectious waste.
15. Write the time on the cassette or set a countdown timer to the required reading time.
16. Read test results after a minimum of xx minutes but no later than xx minutes. Use a good light source when reading the test results.
Venous whole blood from venipuncture
1. Wear gloves.
2. Collect blood by standard venipuncture procedure into a tube containing the correct anticoagulant (EDTA, heparin, oxalate or citrate).
3. Mix the tube gently.
Avoid the tip or center of the finger.
Do not use water or any other buffer than the buffer supplied within this kit.
Hold the buffer bottle vertically – this ensures that the drops contain the correct volume of buffer.
Do not read results after xx minutes
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4. Transfer 5 µl of whole blood in the circle well (marked “1”) of the cassette using a precision pipette.
5. Perform steps 12–16 of the previous section (“Capillary whole blood from finger prick”).
Interpretation of the test result
1. After xx but no later than xx minutes: compare the test lines with the presentation in the table below.
2. Where possible, have the results confirmed by a second reader within this time frame.
3. Line intensities may vary from faint to strong intensity.
Consider also a faint test line as a positive result.
4. Record the test results as noted in the table below.
5. Consult the national guidelines for malaria case management to complement the table below.
lIneS THAT yOU See PIcTURe/DRAWIng RecORD THe FOllOWIng ReSUlT TAke THe FOllOWIng AcTIOn
nO line at ‘C’ (= control)
Put figures of all possible line combinations
Invalid
Take a new cassette packaging and repeat the test
Line at ‘C’ and nO other line
Put figures of all possible line combinations
Negative
Line at ‘C’ AND at ‘Pf’
Put figures of all possible line combinations
Positive for Plasmodium falciparum
Line at ‘C’, at ‘Pf’ AND at ‘pan’
Put figures of all possible line combinations
Positive for Plasmodium falciparum (or rarely, a mixed infection with P. vivax, P. ovale and/or P. malariae)
Line at ‘C’ AND at ‘pan’
Put figures of all possible line combinations
Positive for non-falciparum malaria: P. vivax, P. ovale or P. malariae (or, rarely, a mixed infection with these species)
Other line combinations
Put figures of all possible line combinations
Write down the result
Note: the XXX test kit does not differentiate between P. vivax, P. ovale and P. malariae
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limitations of the product, causes of false-negative and false-positive results
ALL mALARIA RDTS HAVe LImITATIOnS In COmmOn
They may occur despite correct storage and test procedure and are related to:
• the general design of the RDT (detection limit, prozone, no quantification)
• the antigen (HRP-2 deletions, HRP-2 persistence after treatment)
• the operator (overlooking faint test lines)
• the species (in general: sensitivity for P. falciparum > P. vivax > P. ovale/malariae).
Other limitations related to the end-user and the conditions during transport and storage. Some limitations are listed below – unless they do not apply for the RDT product under consideration, they should be mentioned.
See also reference “Universal access to malaria diagnostic testing: an operational manual. World Health Organization 2011
malaria RDT have limitations
They may be the cause of:
• false-negative results (no test lines but the patient has malaria)
• false-positive results (test lines visible but the patient does not have malaria)
• invalid test result (no control line and/or incomplete clearing of background)
Sensitivity for detecting malaria is lower in the case of P. ovale and P. malariae.
False-negative results can occur in the following conditions:
• very low antigen concentrations/parasite densities, for instance < 100 parasites/µl. Note that most clinical cases have higher parasite densities.
• very high parasite densities (very exceptional, prozone or high-hook effect) for the HRP-2 antigen
• deletions in the HRP-2 gene resulting in no production of the HRP-2 antigen (of relevance only for mRDTs that detect this antigen, and only significantly present in the Peruvian Amazon)
• high fraction of insterstitial fluid due to “milking” of fingertip
False-positive results can occur – amongst others – in the following conditions:
• rheumatoid factors, antinuclear antibodies, human anti-mouse antibodies
• viral infection (such as hepatitis B or hepatitis C, dengue)
• parasitic infection (such as schistosomiasis and trypanosomiasis)
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Invalid tests and problems of background clearing may occur:
• In lipaemic and icteric specimens
Note: The presence of the control line only means that migration of added liquid occurred. It does not guarantee that:
• the correct specimen has been used
• the specimen has been applied correctly
• the specimen and test have been correctly stored
• the test procedure was followed correctly
Performance specifications
ReCOmmenDATIOnS fOR DIAGnOSTIC PeRfORmAnCe SPeCIfICATIOnS
• State at least the following specifications and information:
1. Analytical sensitivity (detection limit)
2. Analytical specificity (rheumatoid factor, antinuclear antibody, other infections and influence of lipemic/icteric/hemolyzed specimens)
3. Diagnostic sensitivity
4. Diagnostic specificity
5. Repeatability (test-related, laboratory conditions)
6. Reproducibility (operator-related, field conditions)
• Give enough detail and oversight:
• the numbers of specimens used (and if applicable, confidence intervals)
• the different specifications for P. falciparum, P. vivax, P. ovale and P. malariae
• type of study and setting, geographic place, study period and population
(e.g. laboratory study on stored specimens, clinical study, field study)
• parasite densities and reference methods when appropriate
• present results in a clear way (e.g. table)
• refer to type of study (in-house study, external study, study report or published in scientific literature)/include a bibliography/reference list
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Product-related publications
• Test kit evaluations (product related studies)
general publications
• Biosafety and sampling
• WHO reference documents
• Description of problems on RDT implementation, end-user errors
contact of manufacturer
Name of the legal manufacturer
Full physical address of the manufacturing site (street, city, zip code, country)
Contact for technical assistance ( telephone/fax number, email address)
version number of IFU and date of issue
XXXXX – Language (En, Esp, Fr, etc.) – YYYY/MM/DD
Symbol key
ReCOmmenDATIOnS fOR BIBLIOGRAPHy
• Select relevant publications in a practical and product-oriented way.
• In Annex 3, some references for relevant topics are provided.
bibliogaphy
ReCOmmenDATIOnS fOR SymBOL Key
• Only use internationally recognized symbols.
• In Annex 4, an example of a symbol key is provided.
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Annex 1: ReFeRenceS FOR ReADAbIlITy
The following websites explain how to assess and calculate readability – the tool is primarily developed for English texts.
• http://www.online-utility.org/english/readability_test_and_improve.jsp
• http://www.mang.canterbury.ac.nz/writing_guide/writing/flesch.shtml
Readility can also be assessed in a Microscoft Word document:
1. Click the File tab, and then click Options
2. Click Proofing
3. Under “When correcting spelling and grammar in Word”, make sure the “Check grammar with spelling check” box is selected
4. Select “Show readability statistics” and click on “OK”
After you enable this feature, open a file that you want to check, and check the spelling. When Outlook or Word finishes checking the spelling and grammar, it displays information about the reading level of the document.
Annex 2: ReSOURceS
generic and product specific job aids for Pf –only and combination RDT
Refer to the following websites:
• Generic: http://who.int/malaria/areas/diagnosis/rapid-diagnostic-tests/job-aids/
• Product specific: https://www.finddx.org/implementation-resources/
generic RDT training manual
How to use a rapid diagnostic test (RDT): a guide for training at a village and clinic level 2009.
Universal access to malaria diagnostic testing: an operational manual. World Health Organization 2011
• http://www.who.int/malaria/publications/atoz/9789241502092/en/
Annexes
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Annex 3: exAmPle OF bIblIOgAPHy
Product-related publications
• Test evaluations (product related study)
general publications
• Biosafety and sampling
1. Clinical and Laboratory Standards Institute. Procedures and devices for the collection of diagnostic capillary blood specimens; approved standard, fifth edition. CLSI H04-A6, Vol. 28, No. 25, 2008.
2. Clinical and Laboratory Standards Institute. Procedures for the collection of diagnostic blood specimens by venipuncture; approved standard, sixth edition. CLSI H03-A6, Vol. 27, No. 26, 2007
3. World Health Organization: Laboratory biosafety manual, third edition. Geneva: WHO; 2004. http://www.who.int/csr/resources/publications/biosafety/Biosafety7.pdf
• WHO reference documents
1. World Health Organization: Good practices for selecting and procuring rapid diagnostic tests for malaria. Geneva: WHO; 2011. http://www.who.int/malaria/publications/atoz/9789241501125/en/
2. World Health Organization: Guidelines for the treatment of malaria. Third edition. Geneva: WHO; 2015. http://www.who.int/malaria/publications/atoz/9789241549127/en/
3. World Health Organization: Malaria Rapid Diagnostic Test Performance; Results of WHO product testing of malaria RDTs: Rounds 1–7 (2008–2016). Geneva: WHO; 2017. http://apps.who.int/iris/bitstream/10665/258597/1/9789241512916-eng.pdf
4. World Health Organization: Malaria RDT job-aids and training manuals. http://www.who.int/malaria/areas/diagnosis/rapid-diagnostic-tests/job-aids/en/
5. World Health Organization: Management of severe malaria – A practical handbook. Third edition. Geneva: WHO; 2013. http://www.who.int/malaria/publications/atoz/9789241548526/en/
6. World Health Organization: Transporting, storing and handling malaria rapid diagnostic tests at central and peripheral storage facilities. Geneva: WHO; 2009. http://www.who.int/malaria/publications/atoz/malaria_rdt_central_2009.pdf
7. World Health Organization: Universal access to malaria diagnostic testing. An operational manual. Geneva: WHO; 2011. http://www.who.int/malaria/publications/atoz/9789241502092/en/
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• Description of problems on RDT implementation, end-user errors (included prozone, buffer substitution, false positive,…)
1. Gamboa D, Ho M, Bendezu J, Torres K, Chiodini P, Barnwell J, Incardona S, Perkins M, Bell D, McCarthy J, Cheng Q: A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS One 2010, 5:e8091. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008091
2. Gillet P, Scheirlinck A, Stokx J, De Weggeleire A, Chauque H, Canhanga O, Tadeu B, Mosse C, Tiago A, Mabunda S, Bruggeman C, Bottieau E, Jacobs J: Prozone in malaria rapid diagnostics tests: how many cases are missed? Malar J 2011, 10:166. http://www.malariajournal.com/content/10/1/166
3. Gillet P, Mori M, Van Den Ende J, Jacobs J: Buffer substitution in malaria rapid diagnostic tests causes false-positive results. Malar J 2010, 9:215 http://www.malariajournal.com/content/9/1/215
4. Maltha J, Gillet P, Cnops L, Van Den Ende J, Van Esbroeck M, Jacobs J: Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines. Malar J 2010, 9:198. http://www.malariajournal.com/content/9/1/198
5. Maltha J., Gillet P., Jacobs J. Review: Malaria rapid diagnostic tests in endemic settings. Clin Microbiol Infect 2013; 19: 399–407. http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12151/pdf
6. Maltha J., Gillet P., Jacobs J. Review: Malaria rapid diagnostic tests in travel medicine. Clin Microbiol Infect 2013; 19: 408–415. http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12152/pdf
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Annex 4: exAmPle OF SymbOl legenD
SymbOl exPlAnATIOn SymbOl exPlAnATIOn
In vitro diagnostic medical device Product code
Σ Content sufficient for < n > tests
Consult instructions for use
Lot number Use by YYYY-MM-(DD)
Date of manufacture YYYY-MM-(DD) Manufacturer
Do not reuse Do not use if packaging is damaged
Temperature limitation Lower limit of temperature
Sterile Upper limit of temperature
Irritant Biological risk
Keep away from sunlight Keep dry
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