इंटरनेट मानक

Disclosure to Promote the Right To Information

Whereas the Parliament of India has set out to provide a practical regime of right to
information for citizens to secure access to information under the control of public authorities,
in order to promote transparency and accountability in the working of every public authority,
and whereas the attached publication of the Bureau of Indian Standards is of particular interest
to the public, particularly disadvantaged communities and those engaged in the pursuit of
education and knowledge, the attached public safety standard is made available to promote the
timely dissemination of this information in an accurate manner to the public.

“जान1 का अ+धकार, जी1 का अ+धकार” “प0रा1 को छोड न' 5 तरफ”

Mazdoor Kisan Shakti Sangathan Jawaharlal Nehru
“The Right to Information, The Right to Live” “Step Out From the Old to the New”

IS 13890 (1994): Haemodialysers, Haemofilters and

Haemoconcentrators [MHD 6: Thoracic and Cardiovascular
Surgery Instruments]

“!ान $ एक न' भारत का +नम-ण”

Satyanarayan Gangaram Pitroda
“Invent a New India Using Knowledge”

“!ान एक ऐसा खजाना > जो कभी च0राया नहB जा सकता ह”

है”
ह
Bhartṛhari—Nītiśatakam
“Knowledge is such a treasure which cannot be stolen”
 IS 13890 : 1994
IS0 8637 : 1989

( Reaffirmed 2005 )

Indian Standard
HAEMODIALYSERS, HAEMOFILTERS AND
HAmEMOCONCENTRATORS - SPECIFICATION

UDC 615’47 : 615’38

@ BIS 1994

SUREAU OF INDIAN STANDARDS

MANAK BHAVAN, 9 BAHADUR SHAH ZAFAR MARG
NEW DELHI 110002

Februery 1994 Price Group 8

Thoracic and Cardiovascular Surgery Instruments Sectional Committee, MHD 6

NATIONAL FOREWORD
This Indian Standard which is identical with IS0 8637 : 1989 ‘H-aemodialysers, haemofilters and
haemoconcentrators’ issued by the international Organization for Standardization, was adopted
by the Bureau of Indian Standards on the recommendation of the Thoracic and Cardiovascular
Surgery Instruments Sectional Committee and approval of the Medical Equipment and Hospital
Planning Division Council.

This Indian Standard covers the requirements for medical devices intended for single use for
haemodialysis, haemofiltration and haemoconcentration in humans with a view to ensure their
safety and satisfactory function.
It has not been found practicable to specify materials of construction nor to give test methods
for biocompatibility, validation of sterility, non-pyrogenicity and certain performance character-
istics for haemodialysers, haemofilters and haemoconcentrators. This standard, therefore
requires that the materials have been tested and that the test methods and results are made
available upon request. There is no intention to specify, or to set limits on the performance
characteristics of the devices because such restrictions are unnecessary for the qualified user
and would limit the alternatives available when choosing a device for a specific application.
The dimensions of the blood ports and the dialysing fluid or filtrate ports have been specified to
ensure compatibility of the device with the extracorporeal blood circuit specified in IS 13898 :
1993 ‘Extracorporeal blood circuit for haemodialysers, haemofilters and haemoconcentrators’.
The design and dimensions have been selected in order to minimize the risk of leakage of blood
and the ingress of air. The dialysing fluid ports will accommodate either Hansen or Wafther
connectors.
The text of the above-mentioned IS0 standard has been approved as suitable for publication as
Indian Standard without deviations. Certain terminology and conventions are, however, not
identical to those used in Indian Standards. Attention is particularly drawn to the following:
a) Wherever the words ‘International Standard’ appear referring to this standard, they
should be read as ‘Indian Standard’.
b) Comma ( , ) has been used as a decimal marker while in Indian Standards, the practice is
to use a point ( . ) as the decimal marker.
In this Indian Standard, the following international standards are referred to. Read in their
respective place the following:
international Standard Indian Standard Degree of
Correspondence

IS0 472 : 1979 Plastics - Vocabulary IS 2828 : 1964 Glossary of terms Technically
used in the plastics industry equivalent
IS0 8638 : 1989 Extracorporeal blood IS 13898 : 1993 Extracorporeal blood Identical
circuit for haemodialysers, haemo- circuit for haemodialysers, haemo-
filters and haemoconcentrators filters and haemoconcentrators

For the purpose of deciding whether a particular requirement of this standard is complied with,
the final value, observed or calculated, expressing the result of a test, shall be rounded off
in accordance with IS 2 : 1960 ‘Rules for rounding off numerical values ( revised )‘. The number
of significant places retained in the rounded off value should be the same as that of the specified
value in this standard.
 IS 13890: 1994
IS0 8637: 1989

Indian Sta-ndard
HAEMODIALYSERS, HAEMOFILTERS AND
HAEMOCONCENTRATORS - SPECIFICATION

1 Scope 3.2 blood compartment volume; volume of the blood

compartment: Volume of blood required to fill the haemo-
This International Standard specifies requirements for haemo- dialyser, haemofilter or haemoconcentrator at a given trans-
dialysers, including those of coil, hollow fibre and parallel plate membrane or mean coil pressure.
design, haemofilters and haemoconcentrators for single use for
humans.
3.3 blood flow rate, 0, B: Quantity of blood flowing through
Materials of construction and test methods for biocompati- the haemodialyser, haemofilter or haemoconcentrator per unit
bility, validation of sterility, non-pyrogenicity and some per- time.
formance characteristics are not specified; the rationale for
these omissions is given in the Introduction. NOTE - The blood flow rate is usually expressed in millilitres per
minute.
This International Standard does not apply to devices as-
sembled and sterilized by the user, the extracorporeal blood cir-
cuit, plasma filters, haemoperfusion devices, vascular access 3.4 clearance, y , c : Net flux of solute across the haemo-
devices, blood pumps, pressure monitors of the extracorporeal di_alyser or haemofilter, calculated using the following
circuit, air detection devices or systems to prepare, maintain or equations, as appropriate :
monitor dialysing fluid.

NOTE - Requirements for the extracorporeal blood circuit for haemo- For haemodialysis, using an open loop
dlalysers, haemofilters and haemoconcentrators are specified in
IS0 8638.

2 Normative references “V
NOTE ~- cllF represents the clearance due to convectton
“A
The following standards contain provisions which, through
reference in this text, constitute provisions of this International
For haemodialysis, using a closed loop
Standard. At the time of publication, the editions indicated
were valid. All standards are subject to revision, and parties to
agreements based on this International Standard areencouraged
to investigate the possibility of applying the most recent editions
of the standards listed below. Members of IEC and IS0 main-
tain registers of currently valid International Standards.

NOTE - It has been found that CJ~~ has to be greater than 2 mlimin to
IS0 472 : 1979, Plastics - Vocabulary.
achieve accurate results

IS0 8638 : 1989, Extracorporeal blood circuit for haemo-

dialysers, haemofilters and haemoconcentrators. For haemofiltration

(3)
3 Definitions

For the purposes of this International Standard, the following In equations (1) and (3), it is necessary to use the same units of
definitions apply.
measurement for CA, cv and cr.

3.1 arterial blood circuit: Portion of the extracorporeal In equations (1) to (3)
blood pathway from the vascular access device of the patient to
the blood inlet of the haemodiaiyser, haemofilter or haemo- b is the slope of linear regression of the natural logarithm
concentrator. of the reservoir concentration over time;

1
Is 13890: 1994

IS0 8637 : 1989

cA is the concentration of solute on the inlet side of the 2 Dialysance measurement is useful for comparing devices in systems
haemodialyser or haemofilter ; where the concentration of the solute in the dialysing fluid entering
the haemodialyser is greater than zero, e.g. in recirculation single-pass
cF is the filtrate concentration ; systems.

cv is the concentration of solute on the outlet side of the 3 Dialysance is equal to the clearance in single-pass systems,
haemodialyser or haemofilter ; i.e. when c’D = 0.

Yl’, is the blood flow rate, in millilitres per minute, at the

inlet of the device; 3.8 dialysate ; dialysing fluid : Solution used to perfuse a
compartment that is separated from the blood in a
Y k.F is the filtrate flow rate (ultrafiltration rate), in millilitres haemodialyser by the semi-permeable membrane.
per minute ;

Ar is the duration of the test, in minutes ft - to), where to

3.9 dialysing fluid compartment volume; volume of the
is the time at the beginning of the test and t the time at the dialysing fluid compartment: Volume of the dialysing fluid
end of the test;
required to fill the dialysing fluid compartment of the haemo-
V. is the volume of the “blood” reservoir, in millilitres, at dialyser at a given transmembrane pressure.
time fn.

NOTES
3.10 dialysing fluid addition rate: Rate at which fresh
dialysing fluid is added to a recirculation single-pass system.
1 The term “ultrafiltration” is commonly used as a synonym for
“filtration” in haemodialysis. NOTE - The dialysing fluid addition rate is usually expressed in
millilitres per minute.
2 Clearance is usually expressed as the number of millilitres of blqod
completely cleared of the solute per minute (corrected for ultra-
filtration).
3.11 dialysing fluid flow rate, 9 td : Rate at which dialysing
fluid enters the haemodialyser.
3.5 clotted residual blood: Residual blood that cannot be
recovered by rinsing the blood compartment.
NOTE - The dialysing fluid flow rate is usually expressed in millilitres
per minute.
3.6 compliance: Change in volume of the blood compart-
ment of the haemodialyser, haemofilter or haemoconcentrator
3.12 dialysing fluid recirculation rate: In coil haemo-
in relation to change in transmembrane pressure.
dialysers, the rate at which dialysing fluid is recirculated
NOTE - Compliance is usually expressed in millilitres per 100
through the device.
millimetres of mercury of transmembrane pressure or mean coil
pressure NOTE - The dialvsrnq fluid recrrculation rate is usually expressed rn
mrllrlitres per mnute.

3.7 dialysance, qv, : Rate of exchange per unit time of a

solute between blood and dialysing fluid per unit ‘blood to 3.13 distributor: Any party other than the manufacturer
dialysing fluid concentration gradient, calculated using the who offers the haemodialyser, haemofilter or haemoconcen-
following equation : trator for sale.

(4) 3.14 filtrate: Fluid removed from the blood compartment

across the semi-permeable membrane into the dialysate or
where filtrate compartment of a haemodialyser, haemofilter or haemo-
concentrator due to a pressure gradient across the semi-
co is the concentration of the solute entering the
permeable membrane.
haemodialyser ;

the other symbols are as defined in 3.4.

3.15 fluid residual blood: Residual blood that can be
It is necessary to use the same units of measurement for CA, cv recovered by further rinsing of the blood compartment.after
and co. rinsing as recommended by the manufacturer.

NGTES
3.16 haemoconcentration : Treatment whereby extra-
1 Clearance may be derived from dialysance for recirculating dialys-
corporeal blood is passed through a device (the haemoconcen-
ing fluid systems using the following equation :
trator) for the sole purpose of removing fluid from the blood.
(J’D
YIc = - (5) NOTE - In haemoconcentration, blood flows through one part of a
4 i ‘D chamber divided by a semi-permeable membrane. The filtrate passin’g
l+-
through the membrane is collected in the other part of the chamber
4,;
and is led to waste. The permeability of the membrane does not allow
where qrb is the dialysing fluid flow rate. clinically significant loss of protein from the blood.

2
 IS 13890: 1994

~ISO 8637 : 1989

3.17 haemoconcentrator : Device used to perform haemo- 3.25 non-pyrogenic : Free of pyrogenic material within the
concentration. limit of error of test methods for such determinations, as
defined by the national regulatory agency of. the country in
which the device is to be marketed or, where available, an Inter-
3.18 haemodialyser: Device used to perform haemo- national Standard, and maintained in that state by suitable pro-
dialysis. tection.

3.19 haemodialysis : Treatment whereby extracorporeal 3.26 recirculation system : Dialysing fluid system in which
blood is passed through a device (the haemodialyser) that the dialysing fluid is recirculated through the haemodialyser
allows the transfer of substances by diffusion and convection repeatedly during dialysis.
for the purpose of decreasing biochemical abnormalities as well
as fluid, electrolyte and acid-base imbalances. 3.27 recirculation single-pass system : Dialysing fluid
system in which the dialysing fluid is recirculated repeatedly
NOTE - In haemodialvsis, the blood flows through a chamber divided through the haemodialyser during dialysis and the recirculating
by a semi-permeable membrane, on the other side of which flows the
volume is displaced continuously to waste by fresh dialysing
dialysing fluid. Solute exchange between the blood and the dialysing
fluid.
fluid is mainly due to diffusion. Fluid exchange between the blood and
dialysing fluid is mainly due to ultrafiltration. The permeability of the
membrane does not allow clinically significant loss of protein from the 3.28 residual blood: Volume of blood remaining in the
blood. haemodialyser, haemofilter or haemoconcentrator after the
procedure recommended by the manufacturer for returning the
blood from the device to the patient.
3.20 haemofilter : Device used to perform haemofiltration.

NOTE - Residual blood is usually expressed in millilitres

3.21 haemofiltration : Treatment whereby extracorporeal

blood is passed~through a filtration device (the haemofilter) for 329 semi-permeable membrane : Membrane used to
the purpose of decreasing biochemical abnormalities as well as separate blood from dialysing fluid in haemodialysis or through
fluid, electrolyte and acid-base imbalances, which is achieved which filtrate passes in haemofiltration or haemoconcentration.
by the exchange of a filtrate of the blood for an appropriate
volume of a physiological replacement solution. 3.30 single-pass dialysing fluid system : Dialysing fluid
system in which the dialysing fluid flows to waste after one
NOTE - In haemofiltration, the blood flows through a chamber divrded passage through the haemodialyser.
by a semi-permeable membrane on the other side of which flows a
physiological replacement solutron which infuses into the bloodstream
The permeability of the membrane does not allow clinically sign ficant 3.31 sterile : Free from all living organisms within the limits
loss of protein from the blood. of validation tests for sterility and maintained in that state-by
suitable protection.

3.22 hydraulic resistance: Blood or dialysing fluid com-

3.32 transmembrane pressure (TMP), /?TM : Hydrostatic
partment flow resistance measured as the pressure drop, in
pressure exerted across the semi-permeable membrane of
millimetres of mercury, or change in pressure, 11, between inlet
certain haemodialysers (hollow-fibre, parallel-plate, coil with
and outlet ports of the haemodialyser, haemofilter or haemo-
closed dialysate compartment) or a haemofilter, calculated
concentrator at a given flow rate.
using the following equations :

manufacturer: Party that assumes responsibility for For haemodialysis

3.23
quality assurance of the final product.

(7)

3.24 mean coil pressure (MCP). />Mc: Arithmetic mean of

theinlet and outlet pressure of the blood pathway of a coil For haemofiltration
naemodialyser with an open dialysing fluid compartment,
calculated using the following equation :
PTM = PB.i ; PB.o- pF
(81
Pa.1 + PB.0
PMC = where
2
Pd,i is the pressure of dialysing fluid on the inlet side of the
haemodialyser ;

Ps,i is the pressure of blood on the arterial side of the Pd.0 is the pressure of dialysing fluid on the outlet side of
haemodialyser, in millimetres of mercury; the haemodialyser ;
pF is the pressure at the outlet of the filtrate compartment;
pe o is the pressure of blood on the venous side of the
hakmodialyser, in millimetres of mercury. pE,, and pa,o are as defined in 3.24.

3
IS. 13890: 1994

IS0 8637 : 1989

3.33 user: Operator of a device. 4.5 Residues from sterilization

After sterilization by the procedure recommended by the

3.34 venous blood circuit : Extracorporeal blood circuit manufacturer, the device shall be tested for freedom from toxic
from the outlet of the haemodialyser,. haernofilter or haemo- residues that have adverse chemical, physical or biological
concentrator, returning blood to the vascular access device of effects on the blood or that result in release of clinically signifi-
the patient. cant amounts of potentially toxic substances into the blood. If
requested, details of the test methods and the results shall be
made available by the manufacturer of the device.
4 Requirements
NOTE Attentron is drawn to the need to establish whether national
regulations or natronal standards governing testing for residues from
4.1 Good manufacturing practice sterilization exist in the country rn which the device is produced and, if
applrcable, rn the countnes rn whrch the devrce is to be marketed.
The haemodialyser, haemofilter or haemoconcentrator shall be
Testing shall be carried out in accordance with 5.5.
manufactured in a clean environment and the fluid pathways
shall be free of visible foreign material.
4.6 Mechanical characteristics
NOTE ~ Attention is drawn to the need to establish whether codes for
good manufacturing practice exist in the country in which the device is 4.6.1 Structural integrity
produced and, if appljcable, in the countries in which the devrce is to
be marketed. Samples of the haemodialyser, haemofilter or haemoconcen
trator shall be capable of withstanding 1,5 times the maximum
Testing shall be carried out in accordance with 5.1 transmembrane pressure or mean coil pressure specified by the
manufacturer. Devices with a closed dialysing fluid cornpart-
ment or filtrate compartment shall also withstand a subatmos-
4.2 Toxicology and biological compatibility pheric pressure that is

Samples of the device shall be tested for freedom from toxicity a) 1.5 times the maximum subatmospheric pressure
using, if available, the method specified in the relevant national specified by the manufacturer, or
standard and the results of such tests shall indicate freedom
b) 700 mmHg below atmospheric pressure if the manu
from biological hazard. If requested, details of the test method
facturer’s maximum specified subatmospheric pressure
and the results shall be made available by the manufacturer of
exceeds this value.
the device.
Testing shall be carried out in accordance with 5.6.1.
NOTE Attention IS drawn to the need to establish whether national
regulations or natronal standards governrng toxrcology and brocom-
4.6.2 Membrane integrity
patibility testing exrst rn the country rn which the devrce IS produced
and, if applicable, rn the countries in which the device IS to be A test that will detect a blood leak shall be performed on each
marketed
haemodialyser, haemofilter or haemoconcentrator.

Testing shall be carried out in accordance with 5.2. Testing shall be carried out in accordance with 5.6.2.

483 Blood compartment ports

4.3 Sterility
Except where the haemodialyser, haemofilter or haemoconcen
The fluid pathways of the device shall be supplied sterile. trator and the extracorporeal circuit are designed as an integral
system, the dimensions of the blood ports shall be as given in
NOTE ~ Attentron IS drawn to the need to establish whether national
figures 1 and 2.
regulations or national standards governing sterility testing exist in the
country in which the device is produced and, if applicable, in the The dimensions shall be checked in accordance with 5.6.3.
countries in which the device is to be marketed.

4.6.4 Haemodialyser dialysing fluid compartment ports

Testing shall be carried out in accordance with 5.3.
The dimensions of the dialysing fluid compartment ports shall
be as given in figure 3. In addition, the dialysing fluid compart-
4.4 Pyrogenicity
ment port may have a component that will open a self-seating
connector.
The blood pathway(s) of the device shall be non-pyrogenic. If
requested, details of the test method(s) and the results shall be The dimensions of the dialysing fluid compartment ports shall
made available by the manufacturer of the device. be checked in accordance with 5.6.4.

NOTE - Attention is drawn to the need to establish whether national 4.6.5 Haemofilter or haemoconcentrator filtrate port
regulations or natronal standards governing pyrogen testing exist in the
country in whrch the device is produced and, if applicable, in the The haemofilter or haemoconcentrator filtrate port shall meen
countries in which the devrce is to be marketed.
the requirements specified in 4:6.3 or 4.6.4.

Testing shall be carried out in accordance with 5.4. The filtrate port shall be checked in accordance with 5.6.5.

4
 IS 13890: 1994
IS0 8637: 1989

Dimensions in millimetres

10mm.

1) Double thread.

Figure 1 - Main fitting dimensions of blood inlet and outlet connections

Dimensions in millimetres

As-- $06 :l

8
5,5

Figure 2 - Length of engagement of male and female cones of blood inlet and outlet connectors

5
IS 13890: 1994
IS0 8637: 1989

Dimensions in millimetres

Figure 3 - Main .fitting dimensions of dialysing fluid inlet and outlet port

4.7 Disclosure of performance characteristics The following information shall be given in the product
literature or the product data sheet:

4.7.1 General
a) the number of units tested;

The performance characteristics specified in 4.7.2 to 4.7.6 shall

b) the mean and standard deviation of measurement for
be determined prior to marketing a new type of device and shall
each parameter ;
be re-evaluated after changes in the device that may alter its
performance.
c! the details of change in performance that may occur
with duration of observation ;
The sample of devices shall be drawn at random from the
manufacturer’s production and shall have passed all safety and
d) a statement, If appropriate, that in vitro results are likely
quality control measures, when applicable. They shall be
to differ from in vivo results, with an estimate of the
prepared according to the manufacturer’s recommendations as
magnitude of the dtfference, If known.
though they are to be used for a clinical procedure.

Measurements shall be made in vitro at 37 OC + 1 “C. When

4.7.2 Clearance of haemodialysers
the relationship between variables is non-linear, sufficient
determinations shall be made to permit interpolation between
The clearance rates of urea, creatinine and vitamin B,, shall‘be
the data points. The techniques of measurement are referee
stated for the range of blood and dralysing fluid flow rates
tests. Other techniques may be used provided that the results
recommended by the manutacturer and shall include a blood
are within F 5 % of the technique used in the referee test.
flow rate of 200 ml/min and a dialysing fluid flow rate of
500 ml/min. The filtrate flow rate, (1, F, shall be stated for each
The test systems shown do not indicate all the necessary
condition.
details of practicable test apparatus. The design and construc-
tion of actual test systems and the establishment of actual test
systems shall also address the many factors contributing to The blood compartment s:rall be perfused with the test sub-
measurement error, including, but not limited to, pressure stances dissolved in dialysing fluid. The perfusate shall contain
measurement errors due to static head effects and dynamic the materials within the range specified below :
pressure drops, parameter stabilization time, uncontrolled
temperature variations at the non-constant flow rates, pl-l, Urea : 15 mmolil to 35 mmolil
degradation of test substances due to heat, tight and time, out-
Creatinine : 500 umolil to 1 000 urn-11 I
gassing of test fluids, trapped air, and system contamination by
foreign material, algae and bacteria. Vitamin B,, : 15 ymol!l to 40 umolil

6
 IS 13890: 1994

IS0 8637: 1989

The dialysing fluid compartment shall be perfused with dia- millilitres per hour. The priming pressure shall not exceed the
lysing fluid. In the case of coil haemodialysers, dialysance shall maximum test pressure.
not be substituted for clearance and, if the former is given in
addition, the relationship between the two and the clinical Measurements shall be performed with dialysing fluid perfusing
relevance of clearance shall be emphasized. In addition, the the blood compartment, and, in the case of haemodialysers, no
recirculation rate through the coil haemodialyser shall be fluid perfusing the dialysing fluid compartment. The sequence
stated. of measurement shall be from minimum to maximum trans-
membrane pressure or mean.coil pressure.
NOTE -- Examples of suitable test circuits are given in figures 4 to 8.
NOTE - Examples of suitable test circuits are given in figures 8 and 9.

4.7.3 Clearance for haemofilters

4.7.5 Volume of blood compartment

The clearance rate of urea, creatinine and vitamin B12 shall be The volume of the blood compartment and, if applicable, the
stated for the range of blood flow rates recommended by the dialysing fluid compartment shall be determined with wetted
manufacturer and shall include a blood flow rate of 200 ml/min. membranes (i.e. a device prepared ds recommended by the
The composition of the solution perfusing the blood compart- manufacturer for clinical use) using non-ultrafiltratable liquid,
ment shall be as specified in 4.7.2. and shall be given at stated conditions over the range of trans-
membrane pressure or mean coil pressure recommended by the
NOTE - An example sf a suitable test circuit is given in figure 8
manufacturer.

4.7.4 Filtration rate 4.7.6 Hydraulic resistance

If the relationship between filtration rate and transmembrane The hydraulic resistance of the blood compartment and, if ap-
pressure or mean coil pressure is non-linear, the filtration rate, plicable, the dialysing fluid compartment shall be determined
expressed in millilitres per hour, shall be given over the using a 32 % ( V/ VI solution of glycerol and water respectively.
manufacturer’s stated range of transmembrane pressure or These measurements shall be carried out over the range of
mean coil pressure. If there is a linear relationship between blood flow rate, dialysing fluid flow rate and transmembrane
filtration rate and the transmembrane pressure or me&r coil pressure or mean coil pressure recommended by the manu-
pressure, the filtration coefficient shall be stated, expressed in facturer.

7
IS 13890: 1994
IS0 8637: 1989

Pressure
controller

P B.0
Pd,o

8
Pd,i

Dlalyslng fluid
supply system
Blood pump I I Dialysing fluid
negative pressure
source

P
F?
--L
--.

Test solution
reservoir

Waste

Waste

NOTE - For explanation of symbols. see 3.24 and 3.32.

Figure 4 - -Diagram of open-loop system for measuring clearance in parallel-plate or hollow-fibre haemodialyser

8
 IS 13890: 1994

IS0 8637: 1989

Pressure
controller

I
I

‘E3,i 8
Dialysing fluid
supply system
Dialysing fluid
negative pressure
device

Test solution
reservoir

Waste

NOTE - For explanation of symbols, see 3.24 and 3.32.

Figure 5 - ~Diagram of closed-loop system for measuring clearance in parallel-plate or hollow-fibre haemodialyser

9
IS 13890: 1994
IS0 8637 : 1989

pO,o

d
Pressure
controller

Fresh dialysing fluid

YI I

Haemodialyser
~Dialysing fluid
t overflow to waste

_
----zI---- --_

Dialysing fluid
recirculation pump

Blood pump

Test solution
reservoir

Waste

NOTE - For explanation of symbols, see 3.24.

Figure-6 - Diagram of open-loop system for measuring clearance in coil haemodialyser

 IS 13890: 1994
Iso 8837: 1989

Fresh dialysing fluid I

Haemodialyser - -

---.
--_
t

--L.
1 Dialysing fluid
overflow to waste

Dialysing fluid
recirculation pump

Blood pump

Test solution
reservoir

NOTE - For explanation of symbok, see 3.24.

Figure 7 - Diagram of closed-loop system for measuring clearance in coil haemodialyser

11
IS 13890: 1994
IS0 8637: 1989

Pressure

-r+
P60

Haemodialyser,
haemofilter or
haemoconcentrator

pB,i

Blood pump

___ ----_-
--- -
Test solution
reservoir

Waste

NOTE - For explanation of symbols, see 3.24.

Figure 8 - Diagram of system for measuring clearance in haemofilter or filtration rate in parallel-plate
or hollow-fibre haemodialyser, haemofilter or haemoconcentrator

12
 IS 13890: 1994
IS0 8637: 1989

pB,~ pB,i
Pressure
controller

I@

Haemodialyser

Blood pump

Test solution
reservoir
Waste

NOTE - For explanation of symbols, see 3.24.

Figure 9 - Diagram of system lor measuring filtration rate in coil haemodialyser

1'3
IS 13890: 1994
IS0 8837: 1989

5 Test methods 5.6.1.2.2 Water, at 37 OC 4 1 OC; if a negative pressure test

(see 5.6.1.5.3) is to be carried out, freshly boiled distilled water
is to be used.
5.1 Good manufacturing practice

Compliance with the requirement specified in 4.1 shall be deter- 5.6.1.3 Apparatus
mined by inspection.
5.6.1.3.1 Extracorporeal circuit, blood pump and stain-
less steel or plastic vessel suitable for use with the plasma
5.2 Toxicology and biological compatibility
(5.6.1.2.1) to’ be used in simulated haemodialysis, haemo-
filtration or haemoconcentration. See IS0 8638.
The toxicology and biological compatibility of materials (of a
device) which will come into contact with biological fluids shall
be determined on samples of each new type of device prior to 5.6.1.3.2 Connectors for the blood ports of the device.
its marketing or after any change in the materials of construc- fitted with tubing capable of withstanding the test pressure(s)
tion of that type of device or after any change in the method of and, if appropriate, suitable for the pressure-generating device
sterilization. (5.6.1.3.6).

NOTE - Testing should be carried out using the method(s) specified in See IS0 8638 for specifications of these connectors.
appropriate national regulations or national standards.

5.6.1.3.3 Connectors for the dialysing fluid or filtrate

5.3 Sterility port(s) fitted with tubing capable of withstanding the test
pressure(s).

The sterilization process shall be validated on samples of the

NOTE - These connectors are for use with devices with closed dlalys-
finished device prior to marketing a new type of device, and,
ing fluid or filtrate compartments.
thereafter, the sterilization process shall be monitored for each
batch.
See IS0 8638 for specifications of these connectors.

5.4 Pyrogenicity
5.6.1.3.4 Fittings designed to close the dialysing compart-
ment when fitted with tubing capable of withstanding the test
Testing for ~pyrogens shall be carried out on samples of each
pressure(s).
new type of device prior to marketing, and, thereafter, the
manufacturer shall perform pyrcpen testing at intervals shown NOTE - These fittings are for use with devices with open dialysing
to ensure non-pyrogenicity of the device. fluid or filtrate compartments.

5.5 Residues from sterilization 5.6.1.3.5 Tubing clamps.

Samples of the finished device shall be tested for potentially 5.6.1.3.6 Device or devices suitable for generating the
toxic residues by recognized toxicological methods prior to required pressure(s).
marketing a new type of device, and, thereafter, the manufac-
turer shall test for toxic residues at intervals shown to ensure
5.6.1.3.7 Pressure gauges, accurate to i- 10 mmHg with a
the safety of the device and after any change of materials of
suitable range of pressure.
construction.

5.6.1.4 Sampling and preparation of test samples

5.6 Mechanical characteristics
A statistically significant sample of devices drawn at random
5.6.1 Structural integrity from the manufacturer’s production which have passed all
safety and quality control measures, where applicable, shall be
The test described shall be carried out prior to marketing a new used. These devices shall be prepared as recommended by the
type of device; it is not intended to be a quality control test. manufacturer for clinical procedures.

5.6.1.1 Principle 5.6.1.5 Procedure

Filling the device with water, followed by subjection of the 5.6.1.5.1 Perfuse the device with plasma (5.6.1.2.1) for 7 h at
device to positive pressure and observation for leaks or other 37 ‘C f 1 ‘C at the maximum pressure gradient across the
faults. If appropriate, subjection of the device to negative semi-permeable membrane recommended by the manu-
pressure and observation for leaks or other faults. facturer.

Assemble the apparatus as shown in figure 10

5.6.1.2 Reagents

Flush the blood and dialysing fluid or filtrate compartments

5.6.1.2.1 Anticoagulated bovine or human plasma, with a with water (5.6.1.2.2) at 37 OC i 1 ‘V, taking care to purge
protein mass concentration of 60 g/l +_ 5 g/l. the system of air.

14
 IS 13890: 1994
IS0 8637: 1989

Pressure gauge

Blood compartment

-------------------

Test fluid source

Dialysing fluid or filtrate compartment
with positive and
negative pressure

NOTE - Haemofilters and haemoconcentrators may have only one port in the filtrate compartment; in the case of haemodialysers with an open
dialysing fluid compartmen?, the ends of the dialysing fluid compartment shall be occluded with caps developed especially for this test.

Figure 10 - Test circuit for mechanical integrity

5.6.1.5.2 Apply a positive pressure I,5 times the manufac- 5.6.2 Membrane integrity
turer’s recommended pressure and seal the apparatus. After
10 min. record the pressure and examine the device visually. Compliance with the requirement specified in 4.6.2 shall be
determined by the procedure recommended by the manufac-
turer. If requested, details of the test and the results shall be
5.6.1.5.3 If appropriate, apply a negative pressure 1.5 times made available by the manufacturer. The validity of the test for
the manufacturer’s recommended pressure and seal the ap- membrane integrity shall be checked prior to marketing a new
paratus unless that negative pressure exceeds 700 mmHg; in type of device in accordance with the method given in
that case, apply a negative pressure of 700 mmHg. After annex A.
10 min, record the pressure and examine the device visually.
5.6.3 Blood compartment ports

5.6.1.6 Expression of results Compliance with the requirement specified in 4.6.3 shall be
determined by inspection.
5.6.1.6.1 Positive pressure test
5.6.4 Haemodialyser dialysing fluid compartment ports
An unsatisfactory test is shown by a decrease in pressure of
more than 1 %, leakage or by a fault in the materials of con- Compliance with the requirement specified in 4.6.4 shall be
struction. determined by inspection,

The results shall be recorded as :‘Pass” or “Fail”. 5.6.5 Haemofilter or haemoconcentrator filtrate port

Compliance with the requirement specified in 4.6.5 shall be

5.6.1.6.2 Negative pressure test determined by inspection.

An unsatisfactory test is shown by a decrease in the negative

pressure of more than 1 %, leakage or by a fault in the 6 Packaging, marking and accompanying
materials of construction. documentation

The results shall be recorded as “Pass” or “Fail”. 6.1 Packaging and marking

6.1.1 Unit containers

5.6.1.7 Test report

At least the following information shall be visible on or through

The test shall be recorded as satisfactory if al! samples pass and
the unit container :
unsatisfactory if any sample fails.

a) the manufacturer’s name and address;

The size of the sample and the rationale for its statistical
significance shall be given. b) the product name;
IS 13890: 1994
IS0 8637: 1989

c) the manufacturer’s identifying code for the device; e) the manufacturet’s maximum recommended trans-
membrane or mean coil pressure (TMP or MCP), as ap-
d) the lot number which will allow the manufacturing plicable ;
history of the device to be traced;
f) the direction of blood flow and dialysing fluid flow, if
e) a statement of sterility and non-pyrogenicity, and applicable.
whether the entire contents of the container or the fluid
pathways only are sterile ; 6.2 Documentation

f) the month and year of sterilization, accurate to within

6.2.1 Accompanying documents
30 days of the actual date of sterilization;
At least the following information shall be supplied with each
g) a statement of single use; outer container:

NOTE -~ Symbol 1051 from IS0 7000 may also be used. a) the manufacturer’s name and address;
8

h) the statement “Read the instructions before use” ; b) the product name;

i) a prominent instruction to prepare the haemodialyser, c) the manufacturer’s identifying code for the device;
haemofilter or haemoconcentrator circuit as directed ;
d) a statement of sterility and non-pyrogenicity and the
method of sterilization ;
j) instructions and warnings regarding storage and
handling.
e) a statement of single use;

NOTE - Symbol 1051 from IS0 7000 may also be used.

6.1.2 Outer containers 8
fl cautions and warnings (see 6.2.3) ;
At least the following information shall appear on the outer
container: g) the recommended practice for anticoagulation ;

a) the manufacturer’s name and address; h) details of any ancillary equipment required ;

i) the generic name and, if applicable, the brand name of

b) the name and address of the distributor, if different
the membrane;
from the information given under a);

j) a general description of the device;

c) the product name, description of contents and number
of devices contained within the outer container; NOTE - This information should include special features such as
filtration Tates requiring special controllers or adverse effects of
d) the manufacturer’s identifying code for the device; bubbles in the dialysing fluid.

e) the lot number which will allow the manufacturing k) the connectors recommended for the dialysing fluid
history of the device to be traced; ports or filtration port;

I) the performance characteristics in accordance with 4.7 ;

f) a statement of sterility and non-pyrogenicity ;

NOTE - If possible, this informatlon should be displayed using

g) the month and year of sterilization, accurate to within graphs of sufficient size to permit Interpolation between values.
30 days of the actual date of sterilization;
m) a statement that the following information is available
h) instructions and warnings regarding handling and to the user on request:
storage.
1) details of the test methods used to obtain the
values used in disclosure of the in vitro performance
6.1.3 Device markings characteristics,

2) the in vivo performance characteristics as specified

The device shall be marked with at least the following infor-
in 4.7 for in vitro data,
mation :
3) the volume of clotted and fluid residual blood,
a) the manufacturer’s name;
4) the generic names of materials of construction, in
accordance with IS0 472 (if applicable),
b) the product name ;
5) the number and size range of particulate matter and
cl the manufacturer’s identifying code for the device; fibres in the effluent from the device when prepared as
recommended by the manufacturer for clinical use, and
d) the lot number which will allow the manufacturing details of the test method used to make this measure-
history of the device to be traced ; ment.

16
 IS 13890: 1994
IS0 8637: 1989

6.2.2 Operating instructions b) dialysing fluid flow rate limitations (applicable only to
haemodialysers) ;
At least the following information shall be given to guide the
user on the appropriate steps for setting up the device : c) blood flow rate limitations;

a) directions for mounting the device in the support, if ap- d) a warning, when appropriate, that due to obligatory
plicable ; filtration, a zero filtration rate cannot be achieved without
a positive dialysing fluid pressure which is hazardous,
b) the positioning of the extracorporeal circuit connection because of the risk of infusing non-sterile dialysing fluid into
and, if appropriate, the positioning of the dialysing flurd the bloodstream and, if relevant, the risk of obstruction of
tubing connections ; the blood pathway(s) by collapse of the membrane;

e) instructions to rinse the device as recommended before

c) the recommended priming, rinsing and termination of
haemodialysis, haemofiltration or haemoconcentration pro- use ;
cedures ;
f) the need for any special equipment;

d) the direction of blood flow, if applicable;

g) a list of known adverse reactions;

e) a typical circuit diagram.

h) a list of general and specific contra-indications, such as
“Not Recommended for Paediatric Use”, “Do Not Use on
6.2.3 Cautions and warnings Non-De-aerated Dialysing Fluid Delivery Systems” ;

At least the following cautions and warnings shall be given i) appropriate warnings and contra-indications of dim-
under 62.1 f) : inished performance if the device is used below certain flow
rates or below a certain pressure or in particular orientations
a) pressure limitations ; (horizontal, vertical, etc.).

17
IS 13890 : 1994
Iso 8637 : 1989

Annex A
(normative)

Test to check validity of membrane integrity test

The test described in this annex shall be carried out prior to A.3.6 System for perfusing the dialysing fluid compart-
marketing the device (see 5.6.2); it is not intended to be a ment with dialysing fluid at 37 T f 1 “C.
quality control test.
NOTE - This system is only required for dialysers.

A.1 Principle
A.4 Sampling and preparation of test
Submission of the device to the non-destructive test used to
samples
detect membrane leaks. Perfusion of the device with blood in
vitro to determine if there is a blood leak.
Astatistically significant sample of devices that have passed all
safety and quality control measures, where applicable, shall be
used. These devices shall be prepared as recommended by the
A.2 Reagent manufacturer for clinical procedures.

A.2.1 Anticoagulated bovine or human blood, Jvith a

hematocrit of 25 % and a protein concentration of A.5 Procedure
60 g/l f 5 g/l at 37 OC f 1 OC.
Displace the fluid in the blood compartment with blood (A.2.1).
A.22 Dialysing fluid, which may be either water at 37 “C
or, if clearance of ions is a concern, a 154 meq/l sodium Recirculate the blood through the blood compartment at the
chloride solution. maximum pressure gradient across the semi-permeable mem-
brane recommended by the manufacturer, using a blood flow
rate that is typical of the blood flow rate during the clinical pro-
A.3 Apparatus cedure.

Examine the dialysing fluid or the filtrate visually for the

A.3.1 Blood pump, as commonly used for clinical haemo-
presence of blood after a period of 30 min.
dialysis, haemofiltration or haemoconcentration.

A.3.2 Stainless steel or plastic vessel for the perfusate. A.6 Expression of results

A.3.3 Heating device, external to the blood pathway and No presence of blood shall be observed.
the vessel of perfusate, capable of maintaining the perfusate at
37 Or: * 1 OC. The results shall be recorded as “Pass” or “Fail”.

A.3.4 Pressure gauges, at least comparable in accuracy

A.7 Test report
to those used for clinical haemodialysis, haemofiltration or
haemoconcentration.
The test shall be recorded as unsatisfactory if any of the
samples fails the test.
A.3.5 Extracorporeal blood circuit, designed for clinical
haemodialysis, haemofiltration or haemoconcentration. See The size of the sample and the rationale for its statistical
IS0 8638. significance shall be given.

18 Printed at Dee Kay Printers, New Qelhi-110015, India