ISO 20069:2019
(Main)Guidance for assessment and evaluation of changes to drug delivery systems
Guidance for assessment and evaluation of changes to drug delivery systems
This document provides guidance for assessment and evaluation of planned changes to drug delivery systems that are integral with, packaged with, or cross-labelled for use with a specified medicinal product. This document is applicable to the drug delivery system's lifecycle from registration clinical studies to end-of-life. This document is applicable to the assessment of changes within the following drug delivery systems: — needle-based injection systems for medical use; — aerosol drug delivery devices; — needle-free injectors for medical use. NOTE These are covered by the ISO 11608 series, ISO 20072 and ISO 21649, respectively. This document might also be useful for assessing and evaluate changes to other drug delivery devices or systems. Examples of changes that are within the scope of this document include but are not limited to the following: a) the same route of administration (e.g. change resulting in including a marketed prefilled syringe to an autoinjector); b) changes to the drug delivery system design (e.g. change in configuration or layout of electrical and mechanical components); c) changes to the medicinal product that affect the drug delivery system; including the primary container closure (e.g. viscosity, particle size); d) changes in production or handling of the drug delivery system (e.g. process scale, manual to automated assembly, glue bond to sonic weld, mould cavitation, sterilization, storage, transportation, work instructions or methods); e) changes in component materials or source of supply; f) changes in software, including changes related to cybersecurity, encryption and connectivity; g) changes in the user interface, including packaging; h) changes to labelling and/or instructions for use. Revisions or additions of software are within the scope of this document. The software can either be integrated into the physical drug delivery system, separate, or both. The applicability of this document to non-integrated software is relevant to the extent that those software changes can impact the drug delivery system and/or impact how users interact with it. Depending on the nature of the change, there can be additional assessments and resulting activities, which can be outside the scope of this document. This document does not provide guidance for defining the objective of the change, nor the various potential opportunities/options for fulfilling this objective.
Gestion des changements d’appareils dans les combinaisons de produits pour l’administration de médicaments
General Information
Standards Content (Sample)
INTERNATIONAL ISO
STANDARD 20069
First edition
2019-08
Guidance for assessment and
evaluation of changes to drug
delivery systems
Gestion des changements d’appareils dans les combinaisons de
produits pour l’administration de médicaments
Reference number
©
ISO 2019
© ISO 2019
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: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 2
3 Terms, definitions and abbreviated terms . 2
3.1 Terms and definitions . 2
3.2 Abbreviated terms . 3
4 Process . 4
4.1 General . 4
4.1.1 Process framework . 4
4.1.2 Quality and risk management . 5
4.1.3 Relationships within the organization and with suppliers or external
organizations . 5
4.2 Phase A — Define and assess . 6
4.2.1 Define change (Figure 1, box 1) . 6
4.2.2 Identify change types (Figure 1, box 2) . 6
4.2.3 Assess impact of change (Figure 1, box 3) . 7
4.3 Phase B — Execute activities . 9
4.3.1 Plan (Figure 1, box 4) . 9
4.3.2 Execute (Figure 1, box 5) . 9
4.4 Phase C — Final evaluation . 9
4.4.1 General. 9
4.4.2 Review data (Figure 1, box 6) .10
4.4.3 Evaluate clinical comparability (Figure 1, box 7) .10
4.4.4 Decision to proceed with change (Figure 1, box 8) .10
Annex A (informative) Templates .11
Annex B (informative) Example of completed templates for assessing and evaluating a change .15
Bibliography .36
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 documents 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).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/patents).
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 84, Devices for administration of medicinal
products and catheters.
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 2019 – All rights reserved
Introduction
This document provides guidance to organizations wishing to implement a systematic approach to
assess and evaluate changes to needle-based injection systems, needle-free injectors and aerosol
delivery devices for medical use (see Clause 1) throughout their lifecycles. In particular, an organization
can use the approach for changes to the drug delivery system from entry into pivotal or registration
clinical studies through the end of commercial supply.
Due to the breadth of potential change circumstances, this document does not contain prescriptive
technical requirements for assessing and evaluating drug delivery system changes but rather provides
illustrative guidance for consideration.
This document does not replace or alter existing statutory and regulatory requirements for assessing
drug delivery system changes.
Prior to using the process outlined in this document, the organization should have determined the
objective of the change including the various opportunities/options for fulfilling the objective.
This document might also be useful for assessing and evaluating change to drug delivery systems other
than needle-based injection systems, needle-free injectors and aerosol delivery devices for medical use.
The process can be applied to multiple product lifecycle stages, including design and development,
production, storage and distribution, installation, servicing and final decommissioning/disposal of
the drug delivery system or associated activities (e.g. up-dating of software). It can also be used by an
organization's suppliers and external parties (e.g. raw materials, components, subassemblies, medical
devices, sterilization services, calibration services, distribution services, maintenance services).
This document is not intended to replace or alter quality management systems, risk management,
or usability engineering requirements in assessing these changes. Rather, it provides a common
framework using a scientific and risk-based approach consistent with
[4]
— ISO 13485 ,
[5]
— ISO 14971 , and
[8]
— IEC 62366-1 .
Although this process focuses on user safety and drug delivery system performance, it also addresses
lifecycle management and includes consideration of appropriate medicinal product guidance (e.g. ICH
Q8, ICH Q9, ICH Q10 and ICH Q12). This will help assess the potential impact of changes on the quality,
safety, and efficacy of the finished product for the target patient population.
Over the course of a finished product's lifecycle, there will be a broad array of drivers for change. These
changes and their various design solutions can be motivated by, but are not limited to the following:
a) adverse event/complaint data;
b) voice of the customer, user feedback or market research;
c) usability studies;
d) changes in processes for production, production scale and supply chain logistics;
e) changes in material or source of supply;
f) impact of changes to the medicinal product that affect the drug delivery system.
This document provides examples of drug delivery system changes using a process flow (see Figure 1).
These examples and the conclusions provided are purely illustrative and are intended to provide
guidance on how to utilize this document.
It is the responsibility of organizations to provide evidence that the approach adopted is commensurate
with the level of risk to ensure the quality, safety and performance of the drug delivery system. While
the focus of this document is the changed drug delivery system, it is also possible that changes to
the medicinal product might impact the drug delivery system (e.g. change in viscosity or volume of
medicinal product resulting in changed drug delivery system performance). It is also possible that
changes to the drug delivery system might impact the medicinal product (e.g. increased injection forces
resulting in changed treatment). As such, one key aspect of this process is assessing the change for
its potential impact on overall quality given the critical interface between the drug delivery system
and the medicinal product. Organizations should evaluate potential impact to the medicinal product
in accordance with relevant regulations and guidelines pertaining to medicinal products (e.g. ICH
guidelines) to ensure the quality, safety and efficacy.
The core of this document is the process flow, which attempts to guide an organization through a risk-
based approach based on drivers of change as mentioned above impacting the
— drug delivery system design,
— manufacturing process, and
— labelling and user interface.
The expectation is that such changes are evaluated through the risk assessment of how the change
could impact system form, fit and function (including medicinal product flow paths) such that users are
not negatively impacted in terms of quality, safety and performance of the drug delivery system. Given
that a single change can affect more than one of the change types (e.g. a material change can also drive
a process change), all change types should be assessed and evaluated.
The identification, analysis, evaluation and control of change are common regulatory requirements
in the post approval phase of a product’s lifecycle, but are also important in the clinical phase of
development. Organizations should demonstrate that as the drug delivery system design evolves, the
link between the drug delivery system and the medicinal product as tested in the clinical setting (for
which market authorization is granted or is intended) is maintained.
vi © ISO 2019 – All rights reserved
INTERNATIONAL STANDARD ISO 20069:2019(E)
Guidance for assessment and evaluation of changes to drug
delivery systems
1 Scope
This document provides guidance for assessment and evaluation of planned changes to drug delivery
systems that are integral with, packaged with, or cross-labelled for use with a specified medicinal
product. This document is applicable to the drug delivery system’s lifecycle from registration clinical
studies to end-of-life. This document is applicable to the assessment of changes within the following
drug delivery systems:
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.