ISO 8637-3:2024

Extracorporeal systems for blood purification - Part 3: Plasmafilters

This document specifies requirements and test methods for plasmafilters, which are devices intended to separate plasma from blood in therapeutic plasmapheresis therapy. This document specifies the requirements for sterile, single-use plasmafilters, intended for use on humans, hereinafter collectively referred to as “the device”, for use in humans. This document does not apply to; - extracorporeal blood circuits; - haemodialysers, haemodiafilters, haemofilters and haemoconcentrators; - haemoperfusion devices; - vascular access devices; - blood pumps; - systems or equipment intended to perform plasma separation. NOTE 1 Requirements for the extracorporeal blood circuit are specified in ISO 8637-2. NOTE 2 Requirements for haemodialysers, haemodiafilters, haemofilters and haemoconcentrators are specified in ISO 8637-1.

Systèmes extracorporels pour la purification du sang — Partie 3: Filtres pour plasma

General Information

• Status: Published
• Publication Date: 30-May-2024
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: ISO/TC 150/SC 2 - Cardiovascular implants and extracorporeal systems
• Drafting Committee: ISO/TC 150/SC 2 - Cardiovascular implants and extracorporeal systems
• Current Stage: 9092 - International Standard to be revised
• Start Date: 13-Oct-2025
• Completion Date: 13-Dec-2025

Relations

• Revises: ISO 8637-3:2018 - Extracorporeal systems for blood purification - Part 3: Plasmafilters
• Effective Date: 25-Feb-2023

Overview

ISO 8637-3:2024 - Extracorporeal systems for blood purification - Part 3: Plasmafilters - specifies requirements and test methods for sterile, single‑use plasmafilters used to separate plasma from blood in therapeutic plasmapheresis. The standard covers device design, performance verification, labelling and packaging for human clinical use, and excludes extracorporeal blood circuits, dialysis/filtration devices, pumps, vascular access and whole-system plasma separation equipment.

Key topics and requirements

This edition defines mandatory topics and test methods (see Clauses 4–6 and 5 respectively). Major technical subjects include:

• Biological safety and haemocompatibility: Evaluation of materials and surfaces that contact blood in accordance with ISO 10993 series.
• Sterility and non‑pyrogenicity: Requirements and verification to ensure blood and filtrate pathways are sterile and non‑pyrogenic.
• Mechanical characteristics: Structural integrity, blood compartment integrity and connector dimensions designed to minimize blood leaks and air ingress.
• Performance characteristics: Measurement and reporting of:
  • Plasma filtration rate
  • Sieving coefficient (solute passage into filtrate)
  • Blood compartment volume
  • Blood compartment pressure drop
  • Haemolytic characteristics
• Transmembrane pressure (TMP): Defined method for calculating mean pressure across the membrane.
• Expiry date, labelling and documentation: Essential labelling on device and containers plus user information to reduce misuse (e.g., inadvertent use for haemofiltration).
• Packaging and sterile barrier validation: Aligned with ISO 11607 requirements.

The standard also prescribes specific test solutions and procedures for validated performance testing (Clause 5).

Practical applications

ISO 8637-3:2024 is used to:

• Guide manufacturers in designing and verifying single‑use plasmafilters for therapeutic plasmapheresis.
• Support quality and regulatory teams preparing technical documentation, sterility validation and biological evaluation data.
• Provide clinicians, procurement and hospital device committees with objective information on device performance (filtration rate, sieving behavior, blood volume and pressure characteristics) for safe selection and clinical use.

Who should use this standard

• Medical device manufacturers of plasmafilters
• Regulatory affairs and quality assurance professionals
• Test laboratories performing haemocompatibility, sterility and performance tests
• Clinical engineers and hospital procurement teams evaluating plasmapheresis devices

Related standards

• ISO 8637-1 and ISO 8637-2 (other parts of the extracorporeal blood purification series)
• ISO 10993 series (biological evaluation)
• ISO 11607 (packaging for terminally sterilized devices)
• ISO 80369-7 / ISO 80369-20 (small‑bore connector specifications and tests)

Keywords: ISO 8637-3:2024, plasmafilters, plasma filter, extracorporeal systems, blood purification, plasmapheresis, haemocompatibility, sterility, sieving coefficient, plasma filtration rate.

Standards Content (Sample)

International
Standard
ISO 8637-3
Second edition
Extracorporeal systems for blood
2024-05
purification —
Part 3:
Plasmafilters
Systèmes extracorporels pour la purification du sang —
Partie 3: Filtres pour plasma
Reference number
ISO 8637-3:2024(en)
© ISO 2024
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
ISO 8637-3:2024(en)
Contents  Page
Foreword .iv
Introduction .v
1 Scope . 1
2  Normative references . 1
3  Terms and definitions . 2
4  Requirements . 3
4.1 Biological safety and haemocompatibility .3
4.2 Sterility .3
4.3 Non-pyrogenicity .3
4.4 Mechanical characteristics .3
4.4.1 Structural integrity.3
4.4.2 Blood compartment integrity .3
4.4.3 Connectors .4
4.5 Performance characteristics .5
4.5.1 Plasma filtration rate .5
4.5.2 Sieving coefficient .6
4.5.3 Blood compartment volume .6
4.5.4 Blood compartment pressure drop .6
4.5.5 Haemolytic characteristics .6
4.6 Expiry date .6
5 Test methods . 6
5.1 General .6
5.2 Biological safety and haemocompatibility .7
5.3 Sterility .7
5.4 Non-pyrogenicity .7
5.5 Mechanical characteristics .7
5.5.1 Structural integrity.7
5.5.2 Blood compartment integrity .7
5.5.3 Connectors .8
5.6 Performance characteristics .11
5.6.1 Test solution .11
5.6.2 Plasma filtration rate — Test procedure .11
5.6.3 Sieving coefficient .11
5.6.4 Blood compartment volume . 13
5.6.5 Blood compartment pressure drop . 13
5.6.6 Haemolytic characteristics . 13
5.7 Expiry date .14
6  Labelling . 14
6.1 Labelling on the device.14
6.2 Labelling on unit containers . 15
6.3 Labelling on the outer containers . 15
6.4 Information to be given in the accompanying documentation .16
7  Packaging. 17
Bibliography .18

iii
ISO 8637-3:2024(en)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out through
ISO technical committees. Each member body interested in a subject for which a technical committee
has been established has the right to be represented on that committee. International organizations,
governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely
with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are described
in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the different types
of ISO document should be noted. This document was drafted in accordance with the editorial rules of the
ISO/IEC Directives, Part 2 (see www.iso.org/directives).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and expressions
related to conformity assessment, as well as information about ISO's adherence to the World Trade
Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www.iso.org/iso/foreword.html.
This document was prepared by Technical committee ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This second edition cancels and replaces the first edition (ISO 8637-3:2018), which has been technically
revised.
The main changes are as follows:
— terms and definitions have been aligned with those defined in other parts of the ISO 8637 series;
— additional figures relating to a gauge to test dimensional compliance of connectors have been added;
— test methods for measurement of the sieving coefficient and haemolytic characteristics have been
revised;
— requirements for accompanying documentation have been revised and extended to ensure that the risk
of inadvertent use of a plasmafilter for haemofiltration is minimized.
A list of all the parts in the ISO 8637 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.

iv
ISO 8637-3:2024(en)
Introduction
This document is concerned with filters intended to perform plasma filtration in humans. If such a filter
is used with an extracorporeal circuit, the dimensions of the blood compartment connectors and filtrate
compartment connectors have been specified to ensure compatibility of the device with the extracorporeal
blood circuit specified in ISO 8637-2. The design and dimensions have been selected to minimize the risk of
leakage of blood and the ingress of air.
It was not found practicable to specify materials of construction. Therefore, this document only requires
that materials used have been tested, and that the testing methods and the 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.

v
International Standard ISO 8637-3:2024(en)
Extracorporeal systems for blood purification —
Part 3:
Plasmafilters
1 Scope
This document specifies requirements and test methods for plasmafilters, which are devices intended
to separate plasma from blood in therapeutic plasmapheresis therapy. This document specifies the
requirements for sterile, single-use plasmafilters, intended for use on humans, hereinafter collectively
referred to as “the device”, for use in humans. This document does not apply to;
— extracorporeal blood circuits;
— haemodialysers, haemodiafilters, haemofilters and haemoconcentrators;
— haemoperfusion devices;
— vascular access devices;
— blood pumps;
— systems or equipment intended to perform plasma separation.
NOTE 1 Requirements for the extracorporeal blood circuit are specified in ISO 8637-2.
NOTE 2 Requirements for haemodialysers, haemodiafilters, haemofilters and haemoconcentrators are specified in
ISO 8637-1.
2  Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes
requirements of this document. For dated references, only the edition cited applies. For undated references,
the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-4, Biological evaluation of medical devices — Part 4: Selection of tests for interactions with blood
ISO 10993-7, Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals
ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile
barrier systems and packaging systems
ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for forming,
sealing and assembly processes
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors for
intravascular or hypodermic applications
ISO 80369-20, Small-bore connectors for liquids and gases in healthcare applications — Part 20: Common
test methods
ISO 8637-3:2024(en)
ISO 20417, Medical devices — Information to be supplied by the manufacturer
3  Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
blood compartment
part of the plasmafilter (3.7) through which blood is intended to pass
3.2
blood compartment volume
volume which is needed to fill the blood compartment (3.1)
Note 1 to entry: For hollow fibre devices, the blood compartment volume includes the volume of the hollow fibres plus
the headers.
3.3
plasma filtrate compartment
part of the plasmafilter (3.7) through which filtrate flows
3.4
plasma filtration rate
rate at which plasma is removed from the blood compartment (3.1) across the semipermeable membrane
into the plasma filtrate compartment (3.3) of a plasmafilter (3.7)
3.5
labelling
written, printed, graphic or electronic matter that is affixed to the plasmafilter (3.7) or any of its containers
or wrappers, or that accompanies a plasmafilter, and which is related to the identification, technical
description and use of that device, excluding shipping documents
3.6
plasma separation
plasmapheresis
plasma filtration
separation of a portion of the whole plasma from formed elements of blood by means of a semipermeable
membrane
Note 1 to entry: Plasma separation can also be accomplished through the use of centrifugation; however, this method
is not covered by this document.
3.7
plasmafilter
plasma separator
device intended to perform membrane plasmapheresis (3.6)
3.8
sieving coefficient
ratio of a solute concentration in the filtrate to the simultaneous concentration of the same solute on the
feed side
ISO 8637-3:2024(en)
3.9
transmembrane pressure
TMP
p
TM
mean pressure exerted across the semipermeable membrane contained in the plasmafilter (3.7)
Note 1 to entry: The transmembrane pressure is given by Formula (1):
pp+
BI BO
p = − p (1)
TM F
where
p is the pressure at the blood compartment inlet;
BI
p is the pressure at the blood compartment outlet;
BO
p is the pressure at the filtrate compartment outlet.
F
4  Requirements
4.1  Biological safety and haemocompatibility
Parts of the plasmafilter that are intended to come into direct or indirect contact with blood shall be
evaluated for freedom from biological hazards, in accordance with 5.2.
Attention is drawn to the need to establish whether national regulations or national standards governing
toxicology and biocompatibility testing exist in the country in which the device is produced and, if applicable,
in the countries in which the device is to be marketed.
4.2 Sterility
The blood and filtrate pathways of the plasmafilter shall be sterile. Compliance shall be verified in accordance
with 5.3.
4.3  Non-pyrogenicity
The blood and filtrate pathways of the plasmafilter shall be non-pyrogenic. Compliance shall be verified in
accordance with 5.4.
4.4  Mechanical characteristics
4.4.1  Structural integrity
The plasmafilter external casing shall be capable of withstanding a positive pressure of 1,5 times of the
manufacturer's recommended maximum pressure above atmospheric pressure and a negative pressure not
exceeding 66,7 kPa (500 mmHg) below atmospheric pressure, when tested in accordance with 5.5.1.2 and
5.5.1.3.
4.4.2  Blood compartment integrity
When exposing the blood compartment of the plasmafilter to a validated test procedure performed at
1,5 times of the manufacturer's maximum recommended transmembrane pressure, the blood compartment
shall not leak. Compliance with this requirement shall be verified in accordance with 5.5.2.

ISO 8637-3:2024(en)
4.4.3  Connectors
4.4.3.1  Plasmafilter blood compartment connectors
Except where the plasmafilter and the extracorporeal blood circuit are designed as an integral system, the
dimensions of the blood compartment connectors shall be as given in Figure 1 and Table 1.
Plasmafilter blood compartment functional requirements, such as acceptable leakage rate, minimum
separation force, minimum separation and maximum connection torque shall be defined in accordance
with the manufacturer’s risk management process. The boundary parameters used in tests such as the
torques, the connection and disconnection forces as well as holding times and ambient temperatures must
be considered and defined as part of the manufacturer's risk assessment on the use of the product.
Functional testing shall be performed subject to the manufacturer’s risk assessment. Compliance with this
requirement shall be verified in accordance with 5.5.3.2.
Figure 1 — Cone blood inlet and outlet blood compartment connectors of the plasmafilter

ISO 8637-3:2024(en)
Table 1 — Blood compartment connector dimensions
a b c d
E F G H J K P α β γ
mm mm mm mm mm mm mm ° °
Minimum 10,8 0,85 5,97 — —
10 or 9 or 13 or
Nominal 8 11,0 1,1 6,0 15 15 6:100
more more more
Maximum 11,3 1,35 6,03 — —
Key
E length of tapered region
F length of tapered region
G thread pitch
H root diameter
J crest diameter
K thread crest width
P cone diameter
α angle of thread
β angle of thread
γ dimension taper rate
a
Double thread pitch.
b
Altered upper tolerance to accommodate different components and materials.
c
Revised dimension and tolerances based on existing manufacturing practice.
d
Cone's plane of reference: square A. Dimension measured as a projection on the front face. See Figure 1 (Z).
4.4.3.2  Plasmafilter filtrate compartment connectors
Except when the plasmafilter and its extracorporeal circuit is designed as an integral system, the plasma
filtrate compartment connector shall be as follows:
a) connector design of ISO 8637-1:2023, Figure 2 and Table 2; or
b) Luer lock connector design of ISO 80369-7:2021, Figures B.1 and B.3; or
c) a non-locking connection for direct attachment of the tubing.
If non-locking connectors are used, they shall not separate under an axial force of 25 N applied for 15 s.
Filtrate connector functional requirements, such as acceptable leakage rate, minimum separation
force, minimum separation and maximum connection torque shall be defined in accordance with the
manufacturer’s risk management process. The boundary parameters used in tests such as the torques, the
connection and disconnection forces as well as holding times and ambient temperatures must be considered
and defined as part of the manufacturer's risk assessment on the use of the product.
Functional testing shall be performed subject to the manufacturer's risk assessment.
Compliance with these requirements shall be verified in accordance with 5.5.3.3.
4.5  Performance characteristics
4.5.1  Plasma filtration rate
The plasma filtration rate shall be determined in accordance with 5.6.2. The blood flow rate shall cover the
manufacturers specified range for the plasmafilter (see 6.4).

ISO 8637-3:2024(en)
4.5.2  Sieving coefficient
The sieving coefficients for albumin, immunoglobulin G (IgG), immunoglobulin M (IgM), apolipoprotein B
(apoB) or low density lipoprotein (LDL), or other equivalent indicators shall be determined in accordance
with 5.6.3.
4.5.3  Blood compartment volume
The volume of the blood compartment shall be determined in accordance with 5.6.4.
If the blood compartment volume is stable or constant over the clinical range of pressures, a single
measurement is sufficient. If the blood compartment volume varies with pressure, the blood compartment
volume over the clinical range of pressures shall be established.
4.5.4  Blood compartment pressure drop
The pressure drop of the blood compartment shall be determined in accordance with 5.6.5.
4.5.5 Haemolytic characteristics
The haemolytic characteristics shall be determined in accordance with 5.6.6.
4.6 Expiry date
The biological safety, sterility, performance data and mechanical integrity of the device shall be proven after
storage for a period corresponding to the expiry date. The expiry date can be established with validated
accelerated stability studies or real time aging data. Compliance shall be verified in accordance with 5.7.
5 Test methods
5.1  General
The requirements specified in 4.5 shall be determined prior to marketing a new type of plasmafilter and
shall be re-evaluated after changes in the device that can alter its performance.
For the tests, the device sample size shall be risk-based and shall be capable of demonstrating that the test
results meet the full range of specifications of the manufacturer with statistical confidence.
Configuration of the disposable samples used for the tests shall be representative of the final production
configuration, including sterilization.
Measurements shall be made in vitro at (37 ± 1) °C. When the relationship between variables is nonlinear,
sufficient determinations shall be made to permit interpolation between the data points. The techniques of
measurement given in this document are reference tests. Other test methods may be used, provided they
have been validated and shown to be precise and reproducible.
The test systems shown do not indicate all the necessary details of practicable test apparatus. The design and
construction of actual test systems shall also address factors contributing to measurement e
...