Document: ISO/TC 194/WG 14N 963
Date: 2017-08-24

ISO/TC 194/WG 14 Material characterisation

BRIEF MINUTES AND PROGRESS ACHIEVED AT THE MEETING
on 26 and 27 JULY 2017 IN ARLINGTON, USA
The meeting was chaired by Dr. Ted Heise, US, and was attended by 20 delegates from 7countries.
Dr. Heise summarized the progress on part 18 since the previous meeting in Annapolis, 2016,
noting that it had issued as a CD with balloted votes as follows: 10 for approval, 6 for approvalwith comments, and 13 abstentions. Roughly 400 comments were submitted, and the writingteam had since made revisions to the document and proposed resolutions that were provided tothe WG in preparation for these July meetings.
It was noted that the Analytical Ad Hoc Group had completed its work and provided: 1) a
conclusion that the current state of the art was not sufficiently advanced to allow developing acomprehensive list of substances excluded from the TTC approach; and 2) recommended
language on dealing with uncertainty in chemical characterization analyses. This language has
been added to the latest revision of the part 18 document.
Dr. Heise reported that the writing team has updated part 19 to address WG comments, and therevised document (with observations on WG comments) had been submitted to the Secretariat
earlier in 2017. The document should be processed and taken to the next step toward TR laterin August or in September.
The WG spent the remainder of the two days deliberating on revisions of part 18 proposed by
the writing team (documents ISO/TC 194/WG 14 N 959 and 960; table of comments withproposed observations of secretariat and draft revision of part 18, respectively) to addresscomments submitted with balloting of ISO CD 10993-18. Because time seemed unlikely toallow discussion of all 400 comments, work proceeded on comments related to Clause 3(definitions), Clause 5.2 (AET), Clause 6 (procedure), Annex C (extraction principles), andAnnex D (AET). The WG also deliberated on comments that applied generally to the document.
The WG concluded with a plan to continue review of the remaining comments on ISO CD
10993-18 at the next WG meeting, to be held October 17 and 18, 2017 in Seoul, Korea. Inaddition, the writing team will make further revisions to the document to address the WG
deliberations these two days, and will make the updated document available for discussion ofthese additional revisions at Seoul.
The WG acknowledged that the previous resolution to provide a DIS 10993-18 to the secretariat
by end of November, 2017 at the latest may be difficult to complete, but also acknowledged
willingness to try to meet this goal.
Respectfully submitted,Dr. Ted Heise
Convener ISO/TC 194/WG 14

ISO/CD 10993‐18:2017(E)Start:
Establish patientcontact (6.2.1)

EndISO 10993 does
not applyNoNo

Yes

Assesspatient contact.
Is there direct or indirectcontact between device andpat ient?
(6.2.2)

Does worst possible
pat ient i nt eraction exceed the safet y
threshol d for any chemical
const ituent?
(6.6.2)

Assess thedevice’s likely patientinteraction (extractables profile).
Does the toxicologi cal safety assessment
conclude t hat the extract ables present
an accept able patient
health risk? (6.8.2)

Yes

Establish the device’s worst
possible patient interaction
via compositional profiling(see Figure 2)

Model the device’s likely patient interaction via its
extractables profile. Perform a toxicologi cal safetyassessment of all reported extractabl es. See, forexample, 10993:17(see Figure 3)

Yes

No

Determine the device’s actual patientinteraction via its leachables profile(see Figure 4)

Yes

Assess thedevice’s actual patient interaction.
Does the toxicologi cal safety risk
assessment conclude t hat the adverse user
health effect of the leachables
is acceptable?
(6.10.2)

NoEnd; Chemical Characterization Complete
From a chemical perspecti ve, the device
has been established to present anacceptable patient health risk.
Evaluate safety further using non‐chemicalapproaches as appropriate(6.11.1)

End; Chemical Characterization Complete
The device cannot be establ ished to present
an accept able patient healt h risk.
Evaluate safety using non‐chemical approaches.
Consi der modificati on or rejection of the device.
(6.11.2)

Figure 1 — General chemical characterization processThis multiple‐entry approach is proper and justifiable as the flowchart is constructed such that eachsuccessive step gets closer to establishing the actual clinical patient exposure to leachables and thusgets closer to establishing the actual patient safety risk. Entering the process at an intermediate point

12© ISO 2017 – All rights reserved

ISO/CD 10993‐18:2017(E)Toxicology BasedDecisions

AnalyticalTesting

Information Gathering& Evaluation

Start:
Establish patient
contact (6.2.1)

Assesspatient contact
Is there direct or indirectcontact between device
and patient?
(6.2.2)

NoYes

Gather quantit ativ e information on material s &chemical constit uents (including additives, process
ai ds, manufacturing resi duals) to est ablish device
configuration & materials composit ion.
Establish clinical use (6.3.2)
Generate information (such as material
characterizati on) that is necessary to complete
the dev ice configuration and materials
composition (6.3.3)

Is there aclinically establisheddevice wit h the same
configuration, composition, &clinical use?
(6.4)

Yes

No

Establish the appropriate
safety threshol d (6.5)

Establish the worst case patientinteraction based on exposure to
al l of the device’s chemical
const ituents (6.6.1)

Does worst casepat ient i nt eraction exceed the safet y
threshol d for any chemicalconst ituent?
(6.6.2)

NoYes

Continue to Figure 3End; Chemical Characterization Complete
From a chemical perspecti ve, the dev ice
has been established to present an
acceptable patient health risk.
Evaluate safety further using non‐chemical
approaches as appropriate(6.11.1)

Figure 2 — Compositional profiling process

14© ISO 2017 – All rights reservedAnalytical Testing	

Toxicology BasedDecisions	Information Gathering &Evaluation	
Start:
Establish patient contact(6.2.1)

Assess patientcontact.
Is there direct orindirect contact
between devices& user? (6.2.2)	

ここから下のフローのみで良いと思いますが	No	

End:
ISO 10993 does not
apply

Yes	

Gather quantitative information onmaterials & chemical constituents(including additives, process aids,manufacturing residuals) to establish
devices configuration & materials
composition. Establish clinical use (6.3.2)	

General information(such as materialcharacterization) that is necessary tocomplete the device configuration andmaterials composition (6.3.3)	

Is there a clinicallyestablished device
with the same
configuration,composition, &clinical use?(6.4)	

No	Yes	Is chemical
characterization
for toxicologicalevaluation
continued?	

No	End: Chemical Characterization Complete
From a chemical perspectives, the device has
not been established to present an
acceptable health risk. Evaluate safety further
using biological approaches according to ISO
10993-1.

Yes	
Establish the appropriate
safety threshold (6.5)	

Establish the worst case behavior
based on exposure to all of thedevice’s chemical constituents(6.6.1)	
Does the worst casebehavior exceed thesafety threshold forany chemicalconstituents? (6.6.2)	

Yes	
Continue to Figure 3	

No	

End: Chemical Characterization Complete
From a chemical perspectives, the device has
been established to present an acceptable
health risk. Evaluate safety further using nonchemical approaches as appropriate (6.11.1)