EN ISO 12417-1:2015

SLOVENSKI STANDARD
01-december-2015
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Cardiovascular implants and extracorporeal systems - Vascular device-drug combination
products - Part 1: General requirements (ISO 12417-1:2015)
Kardiovaskuläre Implantate und extrakorporale Systeme - Vaskuläre
Medizinprodukt/Arzneimittel-Kombinationsprodukte - Teil 1: Allgemeine Anforderungen
(ISO 12417-1:2015)
Implants cardiovasculaires et circuits extra-corporels - Produits de combinaison
médicament-dispositif vasculaire - Partie 1: Exigences générales (ISO 12417-1:2015)
Ta slovenski standard je istoveten z: EN ISO 12417-1:2015
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 12417-1
EUROPEAN STANDARD
NORME EUROPÉENNE
October 2015
EUROPÄISCHE NORM
ICS 11.040.40
English Version
Cardiovascular implants and extracorporeal systems -
Vascular device-drug combination products - Part 1:
General requirements (ISO 12417-1:2015)
Implants cardiovasculaires et circuits extra-corporels - Kardiovaskuläre Implantate und extrakorporale
Produits de combinaison médicament-dispositif Systeme - Vaskuläre Medizinprodukt/Arzneimittel-
vasculaire - Partie 1: Exigences générales (ISO 12417- Kombinationsprodukte - Teil 1: Allgemeine
1:2015) Anforderungen (ISO 12417-1:2015)
This European Standard was approved by CEN on 8 August 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 12417-1:2015 E
worldwide for CEN national Members.

Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices . 4

European foreword
This document (EN ISO 12417-1:2015) has been prepared by Technical Committee ISO/TC 150
“Implants for surgery” in collaboration with Technical Committee CEN/TC 285 “Non-active surgical
implants” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by April 2016, and conflicting national standards shall be
withdrawn at the latest by April 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this
document.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 12417-1:2015 has been approved by CEN as EN ISO 12417-1:2015 without any
modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Communities under that Directive and
has been implemented as a national standard in at least one Member State, compliance with the clauses
of this standard confers, within the limits of the scope of this standard, a presumption of conformity
with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
This standard provides a process for managing risks associated with medical devices. Because this
standard describes an ongoing process applicable in part or in all to the Essential Requirements of
Directive 93/42/EEC on medical devices, it is not meaningful to link individual clauses of the standard
to specific corresponding Essential Requirements.
Compliance with all the requirement clauses in this standard will ensure that general aspects of medical
devices related to patient risk and safety have been addressed. For particular medical devices or for
particular safety aspects, additional specific requirements may need to be complied with in order to
meet the essential requirements. With respect to users of medical devices and third persons, additional
specific requirements from other EU Directives may need to be complied with in order to meet Essential
Requirement 1. Relevant harmonized standards may also be used for these purposes.
The risk management processes described in this standard could establish the need for collection of
clinical or other experimental data for risk-benefit evaluation purposes. It does not describe how this
has to be carried out. Relevant harmonized standards may be used for this purpose.
WARNING — Other requirements and other EU Directives may be applicable to a product falling within
the scope of this standard.
Table ZA.1— Correspondence between this European Standard
and Directive 93/42/EEC amended by Directive 2007/47/EEC
Essential Requirements (ERs) Clause(s)/sub-clause(s) Qualifying remarks
of Directive 93/42/EEC of this EN ISO 12417-1
7.1 Clause 5
Clause 8
7.2 Clause 8
9.3
Clause 10
7.3 7.2.4.3
7.2.4.3.2
7.2.4.3.2 g)
7.2.4.3.5
Essential Requirements (ERs) Clause(s)/sub-clause(s) Qualifying remarks
of Directive 93/42/EEC of this EN ISO 12417-1
7.4 7.2.4.3
7.2.4.3.4
7.2.4.3.10
7.2.4.3.12
7.2.4.3.13
7.5 7.2.4.3.4
7.2.4.3.10
7.2.4.3.11
7.2.4.3.16
9.3
7.6 5.2.3 f)
8.1 Clause 9
Clause 10
8.3 5.1
(Design) 7.2.4.2
8.3 Clause 8
(Manufacturing, Packaging) Clause 9
10.1
10.2
11.2 m)
8.4 9.1.1
8.5 8.1
9.2
8.6 9.2
Clause 10
8.7 Clause 11 EN ISO 14630:2012, 11.2 f)
9.1 5.1 a) See specific standards product
requirements for the device part
5.2.3 e)
7.2.4.3.10
9.2 5.1
(Risk of injury) 7.2.4.1
9.2 5.2.2 f)
(Magnetic fields) 5.2.3 g)
7.2.4.3.7
9.2 5.2.1 e)
(Aging) 5.2.2 a)
7.1
7.2.4.3.10
9.3 11.2.1 l)
Essential Requirements (ERs) Clause(s)/sub-clause(s) Qualifying remarks
of Directive 93/42/EEC of this EN ISO 12417-1
13.1 11.2.1 i)
11.3
13.2 Clause 11
13.3 a) 11.2.1 b)
13.3 b) 11.2.1 a), c), d)
13.3 c) 11.2.1 f)
13.3 d) 11.2.1 e)
13.3 e) 11.2.1 h)
13.3 f) 11.2.1 g)
13.3 i) 11.2.1 k)
13.3 j) 11.2.1 i)
13.3 k) 11.2.1 j)
13.3 l) 11.2.1 l)
13.3 m) 11.2.1 f)
13.4 11.3 a), d)
13.5 Clause 11
13.6 a) 11.3
13.6 b) 11.3 e), g), j), k), r)
13.6 c) N/A See EN ISO 14630, 11.3 f)
13.6 e) 11.2 b), e), i), j), k), m)
13.6 f) 11.3 j)
13.6 g) 11.3 o), q)
13.6 l) 11.3 j)
13.6 m) 11.3 a), b), c), f)
13.6 n) 11.3 k)
13.6 q) 11.3 t)
INTERNATIONAL ISO
STANDARD 12417-1
First edition
2015-10-01
Cardiovascular implants and
extracorporeal systems — Vascular
device-drug combination products —
Part 1:
General requirements
Implants cardiovasculaires et circuits extra-corporels — Produits de
combinaison médicament-dispositif vasculaire —
Partie 1: Exigences générales
Reference number
ISO 12417-1:2015(E)
©
ISO 2015
ISO 12417-1:2015(E)
© ISO 2015, Published in Switzerland
All rights reserved. Unless otherwise specified, 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
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Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved

ISO 12417-1:2015(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 2
3 Terms and definitions . 2
4 Intended performance . 6
4.1 General . 6
4.2 Classification . 6
4.3 Intended clinical location . 6
5 Design attributes . 6
5.1 General . 6
5.2 Drug-containing part of the VDDCP (DCP) . 7
5.2.1 General. 7
5.2.2 Matrix . 7
5.2.3 Active pharmaceutical ingredient (API) . 7
6 Materials . 8
7 Design evaluation . 8
7.1 General . 8
7.2 Pre-clinical evaluation . 9
7.2.1 Sampling. 9
7.2.2 Conditioning of test samples . 9
7.2.3 Pre-Clinical in vitro test reports and additional information . 10
7.2.4 Pre-clinical in vitro evaluation . 10
7.2.5 Preclinical in vivo evaluation . 16
7.3 Clinical evaluation .21
7.3.1 Purpose .21
7.3.2 Specific aims .21
7.3.3 Clinical investigation plan .21
7.3.4 Data acquisition .22
7.3.5 Final report .24
7.4 Post-market surveillance .25
8 Manufacturing .25
8.1 General .25
8.2 Raw material reporting and analysis of the API .25
8.3 Raw material analysis and reporting for excipients .26
8.4 VDDCP batch release testing .27
9 Sterilization .27
9.1 Products supplied sterile .27
9.1.1 Testing to support “Sterile” labelling .27
9.2 Products supplied non-sterile.27
9.3 Sterilization residuals .27
10 Packaging .27
10.1 General .27
10.2 Considerations for VDDCPs .28
10.3 Impact of changes in storage and shipping temperatures on VDDCP .28
11 Information supplied by the manufacturer .28
11.1 General .28
11.2 Labelling .28
11.2.1 VDDCP label(s) .28
11.2.2 Record label . .29
ISO 12417-1:2015(E)
11.3 Instructions for use (IFU) .29
Annex A (informative) Definitions of potential clinical and technical events .31
Annex B (informative) Local information regarding submission issues for VDDCPs .36
Bibliography .43
iv © ISO 2015 – All rights reserved

ISO 12417-1:2015(E)
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 on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
ISO 12417 consists of the following parts under the general title, Cardiovascular implants and
extracorporeal systems — Vascular device-drug combination products:
— Part 1: General requirements
— Part 2: Local regulatory guidance
ISO 12417-1:2015(E)
Introduction
This part of ISO 12417 was prepared in order to provide minimum requirements for vascular device-
drug combination products (VDDCPs).
Only issues related to vascular devices combined with drug(s), wherein the drug serves an ancillary
function of the VDDCP are covered by this part of ISO 12417.
It was impossible, when writing this part of ISO 12417, to take into consideration all future and
emerging technologies. VDDCPs using such technologies will need to be evaluated following the basic
requirements of this International Standard. Testing beyond the scope of this part of ISO 12417 might
also be necessary to characterize these device systems. Consideration shall be given to the failure
modes of the VDDCP and their effects on the performance in deciding what testing will be appropriate.
For issues related to the primary mode of action (PMOA) of the vascular VDDCP, the reader might find it
useful to consider a number of other International Standards (see Bibliography).
vi © ISO 2015 – All rights reserved

INTERNATIONAL STANDARD ISO 12417-1:2015(E)
Cardiovascular implants and extracorporeal systems —
Vascular device-drug combination products —
Part 1:
General requirements
1 Scope
This part of ISO 12417 specifies requirements for vascular device-drug combination products (VDDCPs)
based upon current technical and medical knowledge. VDDCPs are medical devices with various clinical
indications for use in the human vascular blood system. A VDDCP incorporates, as an integral part,
substance(s) which, if used separately, can be considered to be a medicinal substance or product (drug
substance, drug product) but the action of the medicinal substance is ancillary to that of the device and
supports the primary mode of action (PMOA) of the device. With regard to safety, this part of ISO 12417
outlines requirements for intended performance, design attributes, materials, design evaluation,
manufacturing, sterilization, packaging, and information supplied by the manufacturer. For implanted
products, this International Standard should be considered as a supplement to ISO 14630, which
specifies general requirements for the performance of non-active surgical implants. This International
Standard should also be considered as a supplement to relevant device-specific standards, such as the
ISO 25539-series specifying requirements for endovascular devices. Requirements listed in this part of
ISO 12417 also address VDDCPs that are not permanent implants.
NOTE Due to variations in the design of combination products covered by this part of ISO 12417 and due
to the relatively recent development of some of these combination products, acceptable standardized in vitro
test results and clinical study results are not always available. As further scientific and clinical data become
available, appropriate revision of this part of ISO 12417 might be necessary.
Delivery systems or parts of the delivery system are included in the scope of this part of ISO 12417, if
they comprise an integral component of the vascular device and if they are drug-covered (e.g. drug-
covered balloon catheters and drug-covered guidewires).
Devices whose PMOA is to provide a conduit for delivery of a drug, are excluded from the scope of this
part of ISO 12417 (e.g. infusion catheters), unless they contain a drug component that is intended to
have an ancillary action to the device part (e.g. antimicrobial coated infusion catheter).
Procedures and devices used prior to and following the introduction of the VDDCP (e.g. balloon
angioplasty devices) are excluded from the scope of this part of ISO 12417 if they do not affect the drug-
related aspects of the device.
This part of ISO 12417 is not comprehensive with respect to the pharmacological evaluation of VDDCPs.
Some information on the requirements of different national and regional authorities is given in Annex B.
Absorbable components of VDDCPs (e.g. coatings) are addressed by this part of ISO 12417 in their
connection with drug-related aspects of the device. Degradation and other time-dependent aspects of
absorbable implants and coatings are not completely addressed by this part of ISO 12417.
NOTE See also ISO/TS 17137 and ASTM F3036-13.
This part of ISO 12417 does not address issues associated with viable or non-viable biological materials
such as tissues, cells, or proteins.
This part of ISO 12417 does not address issues associated with active surgical implants (i.e. implants
that require power not generated by the human body or gravity).
ISO 12417-1:2015(E)
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. 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 10993-2, Biological evaluation of medical devices — Animal welfare requirements
ISO 10993-7, Biological evaluation of medical devices — Ethylene oxide sterilization residuals
ISO 11070, Sterile single-use intravascular introducers, dilators and guidewires
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14630:2012, Non-active surgical implants — General requirements
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971:2007, Medical devices — Application of risk management to medical devices
ISO 15223-1, Medical devices — Symbols to be used with medical device labels, labelling and information to
be supplied — Part 1: General requirements
ISO 25539-2, Cardiovascular implants — Endovascular devices — Part 2: Vascular stents
NOTE See the Bibliography for additional device-specific and regional information about standards and
guidance documents.
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 14630 and the following apply.
NOTE Potential clinical events are defined in Annex A.
3.1
active pharmaceutical ingredient
API
drug
pharmacologically active (drug or medicinal) substance used as a raw material, which is coated on,
bound to or incorporated into the device to achieve an ancillary device function (e.g. minimizing
vascular restenosis)
3.2
batch
quantity of VDDCP at the final stage or pre-final stage of manufacture which has undergone the same
manufacturing cycle, using the same components (e.g. same coating solution, same device size), and
meets the same specifications
3.3
change
alteration to an activity or to the VDDCP to improve or maintain the composition or performance of a
VDDCP
2 © ISO 2015 – All rights reserved

ISO 12417-1:2015(E)
3.4
clinical event
complication, failure, or device-related observation that might be observed with clinical use of a VDDCP
Note 1 to entry: Such events might not have clinical significance and might not be attributable to the VDDCP.
3.5
compendial pharmaceutical reference standard
general term covering reference substances, reference preparations, and reference spectra that are
recognized by a national pharmacopoeia
3.6
device part of the VDDCP
DP
part of the VDDCP intended to treat vascular disease by temporary or long-term intervention
or implantation that does not achieve its PMOA in or on the human body by pharmacological,
immunological, or metabolic means, but might be assisted in its function by such means
3.7
drug assay
biological or chemical method to determine the activity or potency of a substance
3.8
drug product
medicinal product
API, in its final form for administration to the patient (e.g. tablet, solution, spray), that is intended to
prevent, diagnose, or treat disease and that achieves its principal intended action in or on the body by
pharmacological, immunological, or metabolic means
3.9
drug-containing part of the VDDCP
DCP
part of the VDDCP that consists of the API or matrix and associated device interfaces intended to assist
in the PMOA of the device and/or diminish or ameliorate an unintended effect that placement of the
device part might stimulate
Note 1 to entry: Some VDDCPs might have an incorporated medicinal or drug substance primarily intended to
optimize the surface properties of the VDDCP.
3.10
DCP interface
common boundary or interconnection between the various components of the device part(s) and the
drug-containing part(s) of a VDDCP
EXAMPLE
a) the interface between the matrix containing the API and packaging materials with direct DCP contact;
b) the device surface(s);
c) the interface between the matrix and the API.
3.11
delivery system
transport device that physically or mechanically positions the VDDCP and/or the DCP at the intended
anatomic location
EXAMPLE The delivery system of a drug-coated balloon, would position the balloon in the lumen of the
lesion intended to be treated.
ISO 12417-1:2015(E)
3.12
drug content
total labelled amount of API in a VDDCP
Note 1 to entry: Drug content might be expressed as µg/DCP of a certain size.
3.13
drug delivery
local interaction between the VDDCP drug and the in vivo environment, whether the drug is released
from, eluted from, or remains bound to the VDDCP
3.14
drug-related impurity
any substance in the DCP of a VDDCP that is not the API or an excipient
Note 1 to entry: Drug-related impurities might include drug degradation products or degradants, drug-synthesis-
related impurities, isomers of the drug, residual drug solvents, or biologic contaminants (e.g. occurring with
drugs derived from biologic systems).
3.15
drug release characterization
in vitro characterization of the API released from the DCP of a VDDCP over time
EXAMPLE The release might be determined by a drug elution test, and could include a curve shape (or
profile), a drug release rate, or both.
3.16
durability
ability to maintain adequate integrity and robustness during procedural (i.e. access, deployment,
withdrawal), post-procedural, and long-term use (i.e. over time) in accordance with the design
specifications
3.17
efficacy
effectiveness
ability of the VDDCP to achieve the planned and desired physiological result
3.18
evaluate
appraise or analyse qualitatively
3.19
excipient
additional material(s), other than the API, that are intentional components of the drug-containing
part of a VDDCP
EXAMPLE Filler, extender, diluent, wetting agent, solvent, colorant, stabilizer, antioxidant, preservative, pH
maintainer, polymers, adhesives.
3.20
functionality
ability of the VDDCP to perform physically, chemically, and/or mechanically, as designed
Note 1 to entry: Functionality does not include the physiological response to the VDDCP (i.e. efficacy).
4 © ISO 2015 – All rights reserved

ISO 12417-1:2015(E)
3.21
matrix
any organic or inorganic material, other than living cells, intentionally applied by a manufacturer to a
vascular device and designed for the purpose of drug storage, local drug activity at the surface and/or
enabling, retarding, delaying, or modifying drug release
Note 1 to entry: The matrix might: be permanent or temporary (dissolvable, absorbable or degradable); include
surface treatments such as primers; be a coating with or without an API, or consist of multiple excipients and/or
multiple APIs.
3.22
particulates
particles
mobile matter, other than gas bubbles, present on, or arising from the use of the VDDCP
3.23
pharmacokinetics
absorption, distribution, metabolism, and elimination of a drug in vivo
3.24
procedural fluids
blood and serum, saline, and contrast media that come into contact with a VDDCP
3.25
stability studies
tests undertaken according to a prescribed stability protocol to establish, support, or confirm the shelf
life of a VDDCP
Note 1 to entry: Additional guidance on the drug-related aspects of the drug-containing part of the VDDCP can be
found in International Conference on Harmonization Guideline ICH Q1A.
3.26
uniformity of drug content
comparison of the uniformity of the drug content between individual VDDCPs within each batch as
compared to the labelled claim
3.27
vascular device-drug combination product
VDDCP
vascular medical device (PMOA) that incorporates one or more APIs as an integral part (ancillary
mode of action)
3.28
VDDCP deployment
physical or mechanical positioning of the VDDCP so that the drug-containing part is in contact with the
intended anatomic treatment site
Note 1 to entry: The VDDCP might be permanently deployed (e.g. a drug-eluting stent) or temporarily deployed
(e.g. a drug-eluting balloon).
3.29
VDDCP specification
required list of test procedures and appropriate acceptance criteria which are numerical limits, ranges,
or other criteria for the tests described
Note 1 to entry: A specification is a critical quality standard. It establishes the set of criteria to which a VDDCP
has to conform.
Note 2 to entry: Additional guidance on the drug-related aspects of the drug-containing part of the VDDCP can be
found in International Conference on Harmonization Guideline ICH Q6A.
ISO 12417-1:2015(E)
4 Intended performance
4.1 General
The requirements of ISO 14630:2012, Clause 4, shall apply.
4.2 Classification
A VDDCP is a product that is considered to be a medical device but which incorporates, as an integral
part, substances which, if used separately, can be considered to be a medicinal product or drug product.
It is classified as a medical device, provided that the action of the medicinal or drug substance is
ancillary to that of the device, as reflected in the product claim and as supported by the scientific data
provided by the manufacturer of the device.
4.3 Intended clinical location
The intended clinical location shall be identified as one or more of the following:
a) abdominal aorta;
b) arterio-venous shunt for vascular access;
c) carotid;
d) coronary;
e) femoral;
f) iliac;
g) popliteal;
h) intracerebral;
i) renal;
j) thoracic aorta;
k) thoraco-abdominal aorta;
l) tibial;
m) other arterial or venous vessels to be specified.
5 Design attributes
5.1 General
The design attributes to meet the intended performance of the VDDCP shall take into account at least
the following:
a) ability of the device part of the VDDCP (i.e. the device without the API and matrix) to fulfill all
product-specific requirements for the PMOA (e.g. the mechanical function), which are defined in
the device-related standards;
b) ability of the drug-containing part of the VDDCP to fulfill the drug-specific function and
requirements of the VDDCP as defined in 5.2.
6 © ISO 2015 – All rights reserved

ISO 12417-1:2015(E)
5.2 Drug-containing part of the VDDCP (DCP)
5.2.1 General
The design attributes of the VDDCP to meet the intended performance of the DCP shall additionally
take into account at least the following:
a) ability of the DCP to be consistently, accurately, and safely brought into contact with the intended
anatomic treatment site;
b) appropriate physical and chemical compatibility of the DCP interfaces (i.e. the device, the drug, the
matrix, and any packaging with direct DCP contact);
c) appropriate biocompatibility of the DCP;
d) conformance of the DCP to VDDCP specifications at the time of manufacture and after storage;
e) ability of the DCP to deliver or maintain the intended amount of drug safely at the target site in
accordance with the specification of the VDDCP at product release and for the duration of the
labelled shelf life;
f) appropriate interaction between the VDDCP and procedural fluids.
5.2.2 Matrix
The design attributes of the VDDCP to meet the intended performance of the matrix shall additionally
take into account at least the following:
a) ability of the matrix to maintain adequate integrity during procedural use and over time in accordance
with the design specifications (e.g. freedom from significant delamination, flaps, and bare spots);
b) ability of the matrix to maintain adequate resistance to unintended generation of particles;
c) conformance of the matrix to VDDCP specifications at the time of manufacture and after storage;
d) conformance of the matrix dimensions, physical and chemical properties, and other matrix
parameters (e.g. porosity, mass, density, distribution, glass transition temperature, melting
temperature, fragmentation point) to the design requirements;
e) if soluble or degradable, the ability of the matrix to control the release of drug and the interaction
of any solubilized or degradation products with the body (i.e. biocompatibility of the matrix as well
as the degradation products);
f) effect of imaging (e.g. the heating caused by magnetic resonance imaging [MRI]) on the matrix.
5.2.3 Active pharmaceutical ingredient (API)
The design attributes of the VDDCP to meet the intended performance of the API shall additionally take
into account at least the following:
a) conformance of drug content, impurities, and degradants to the API specification on receipt and
after storage and handling of the API during the VDDCP manufacturing process;
b) ability to reproducibly incorporate, as demonstrated by content uniformity, the desired drug and
amount within the VDDCP;
c) ability to apply the drug to the target site in accordance with the VDDCP specification;
d) conformance of drug content, drug impurities, and drug degradants to VDDCP specifications at the
time of manufacture and after storage;
ISO 12417-1:2015(E)
NOTE There might be other impurities, evaluated separately from the drug-related impurities, that
are related to manufacture of the matrix or other components of the VDDCP or come from sterilization or
processing aids, such as monomers, catalysts, residual matrix-related solvents, residual processing solvents,
or matrix-related degradation products or degradants. There also might be other biologic impurities such as
endotoxin, evaluated separately from the drug-related impurities.
e) appropriate interaction between the drug(s) and the matrix and/or the device to which the drug(s)
is(are) applied;
f) appropriate interaction between the drug(s) and the tissue to which the drug(s) is(are) applied;
g) effect of imaging (e.g. MRI) on the drug of a VDDCP (e.g. heating).
NOTE Additional guidance on the drug-related specifications can be found in ICH Q6A as well as in general
and individual monographs of pharmacopoeias of the different regions [e.g. the United States Pharmacopeia
(USP), Japanese Pharmacopoeia (JP) and European Pharmacopoeia (EP)].
6 Materials
The requirements of ISO 14630:2012, Clause 6, shall apply when selecting the API, matrix, and DP
materials used to design the VDDCP (e.g. metals, polymers, drugs).
7 Design evaluation
7.1 General
The requirements of ISO 14630:2012, Clause 7, shall apply.
For the properties outlined in this Clause, a justification shall be provided for the properties that are
not assessed.
Whenever changes are made in materials, construction, configuration, application, or processing methods,
an appropriate risk analysis of the potential impact of the change on the failure modes and performance
of the VDDCP shall be performed. Appropriate testing shall be conducted, as deemed necessary.
NOTE Any alterations, including those that might be considered minor alterations to a VDDCP, a
manufacturing process, or a test procedure might require reporting to local regional authorities.
The use of a control device for comparison can be informative in the evaluation of certain design
attributes relevant to the performance of the VDDCP.
Testing
...